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Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney Disease

† † † Yunshuang Liu,* Hongzhi Li,* Jieting Liu,* Pengfei Han, Xuefeng Li, He Bai,* Chunlei Zhang,* Xuelian Sun,* Yanjie Teng,* Yufei Zhang,* Xiaohuan Yuan,* Yanhui Chu,* and Binghai Zhao*

*Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Medical Research Center, Heilongjiang, People’s Republic of China; and †Clinical Laboratory of Hong Qi Hospital, Mudanjiang Medical University, Heilongjiang, People’s Republic of China

ABSTRACT Diabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and second- ary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db/db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro,cotrans- fection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 39 untranslated region. In conclusion, these results reveal a role for miR-25 in diabetic nephropathy and indicate a potential novel therapeutic target for this disease.

J Am Soc Nephrol 28: ccc–ccc, 2017. doi: https://doi.org/10.1681/ASN.2015091017

Diabetic nephropathy (DN) is a progressive kidney and microRNAs (miRNAs) in the pathogenesis of disease that develops secondary to diabetes, and it is hypertension, which serves as a reminder that the the single most common disorder leading to renal deregulation of miRNA expression plays a key role failure in developing countries.1 The percentage of in hypertension, especially originating from DN.6 individuals with DN in China also exceeds the per- miRNAs are short noncoding RNAs of approxi- centage with CKD related to GN.2 DN is charac- mately 22 nucleotides in length that exert their terized by persistent albuminuria (.300 mg/d), a progressive decline in the GFR, and elevated arte- rial BP.3 BP control and efficient blockade of the Received September 14, 2015. Accepted August 16, 2017. renin-angiotensin system (RAS) to reduce micro- Y.L., H.L., and J.L. contributed equally to this work. albuminuria together with tight glycemic control 4 Published online ahead of print. Publication date available at are important therapeutic strategies for DN. www.jasn.org. However, this strategy is insufficient to prevent progression to renal failure in a substantial propor- Correspondence: Dr. Yanhui Chu or Dr. Binghai Zhao, Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical 5 tion of patients. Thus, novel effective therapeutic University, 3 Tongxiang Street, Mudanjiang, Heilongjiang approaches are critical for the treatment and pre- 157001, People’s Republic of China. Email: yanhui_chu@163. vention of the disease. Intriguingly, recent studies com or [email protected] have shown a link between ACE2/Apelin signaling Copyright © 2017 by the American Society of Nephrology

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canonical function by binding the 39 un- translated region (39UTR) of mRNAs and regulate the expression of 50% of genes.7,8 It is well known that one miRNA can target multiple mRNAs, whereas one mRNA can be bound by a combination of numerous miRNAs.Therefore,miRNAsandtheir target mRNAs form an intricate regulatory network that can be expressed as a recip- rocal “one-to-more” relationship, which has been hypothesized as a “fail-safe” mechanism to control gene expression.9 In mice, a podocyte-specificknockoutof Dicer, an enzyme critical to the miRNA biogenesis pathway, leads to progressive re- nal glomerular and tubular damage.10–12 A similar phenotype is also observed when Drosha is inducibly deleted in podocytes.13 Thus, we conclude that excessive deficiency of miRNAs due to deletion of Dicer and Drosha contributes to renal dysfunction and suggest that dysregulation of miRNAs can promote kidney disease. Emerging ev- idence confirms that individual miRNAs, including microRNA-23b (miR-23b),14 miR-192/216a/217,15,16 and miR-377,17 are involved in DN. Recent studies have also shown that miRNAs, including miR- 143/145, are associated with the pathogen- esis of hypertension.18–20 In this study, we have shown that miR-25 is commonly downregulated in the serum and kidneys of patients with DN, the kidneys of mouse models of type 1 and 2 diabetes, and spe- cific kidney cells exposed to high glucose. We also observed that downregulation of miR-25 in normal mice causes severe renal disease with hypertension, and upregula- tion of miR-25 in db/db mice can reverse DN alterations and reduce high BP.

RESULTS Figure 1. Excessive miR-25 reverse albuminuria and fibrosis in diabetic nephropathy. (A) miR- 25 levels in the sera of patients with type 1 diabetes (T1DM), type 2 diabetes (T2DM), or DN Overexpression of miR-25 Reverses were reduced compared with the healthy controls (Con). (B and C) Similarly, miR-25 was re- Albuminuria and Fibrosis in Diabetes duced in the kidneys of type 1/2 diabetic (Dia [n=5] and db/db [n=5]) animals compared with miR-25 levels in the sera of patients with controls (Con; n=5).(D)miR-25expressionlevelsinvarioustissuesofnormalC57BL/6mice.(E) diabetes both with and without nephropa- fi – Quanti cation of 24-hour albumin excretioninmiR-25agomir treated mice. (F) Representative thyweredownregulatedcomparedwith images of H&E (row 1), PAS (row 2), Sirius Red (row 3), a-SMA (row 4), and TEM (row 5) staining those in healthy controls (Figure 1A). A sim- from kidney sections of miR-25 agomir–injected mice. Green arrows indicate areas of fibrosis, an asterisk indicates the GBM, and a red arrow represents a foot process. (G) Quantification of ilar downregulation of miR-25 occurred as the a-SMA–positive area within glomeruli from miR-25 agomir–treated kidney sections. (H) detected by quantitative PCR (qPCR) in the Quantification of GBM thickening after miR-25 agomir injection. (I) Quantification of foot kidney tissues of streptozotocin-induced di- process fusion from miR-25 agomir–treated db/db mice. (J) Measurement of BP from miR-25 abetic and db/db mice (Figure 1, B and C) agomir–injected db/db mice. Data are shown as the mean6SEM. **P,0.01; ***P,0.001. and cultured cells exposed to high glucose

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Figure 2. Overexpression of miR-25 inhibit RAS activation. (A) Representative images of KRI (row 1), angiotensin 1 (AT1; row 2), renin (row 3), and vWf (row 4) staining from miR-25 agomir–treated db/db mouse kidney sections (right panel represents a quantification of the images). (B) Quantification of an ELISA for serum renin, angiotensin I/II, and aldosterone (ALD) from miR-25 agomir– and antagomir– treated mice. Data are shown as the mean6SEM. Con, control. ***P,0.001.

(Supplemental Figure 1, A–C). We also found that miR-25 in the miR-25 was highly expressed in mouse heart, muscle, adipose serum of db/db mice was decreased significantly compared with tissue, and kidneys compared with other tissues (Figure 1D). in the wild type (Supplemental Figure 1D). To regulate their To establish the functional consequence of miR-25 upregula- target mRNAs, the miRNA minimum threshold of expression tion in the kidneys,we performed intravenous miR-25 agomir must be reached, and the abundance of miRNAs in the miR- (2.5 mg/kg) injection in db/db mice. Delivery efficiencies NAome of a specific cell or tissue may be more important for showed an approximately fourfold increase in kidney miR-25 their function at the organismal level.21 We examined miR-25 expression (Supplemental Figure 1E). Importantly, miR-25 levels in multiple tissues, including the kidneys, and found that agomir injection in db/db mice decreased their proteinuria

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(Figure 1E, Supplemental Figure 1F) and reversed their glomer- (Supplemental Figure 1I). In keeping with these findings, ular fibrosis as shown by H&E, PAS, Sirius Red, and a-SMA mesangial expansion, GBM thickening, and podocyte foot staining (Figure 1, F and G). Furthermore, miR-25 agomir collapse were observed under electron microscopy in miR-25 treatment reversed the upregulation of a series of fibrosis gene antagomir–treated mice but were not observed in the mice re- markers; however, miRNEG treatment had no such effect ceiving miRNEG injections (Figure 3, D and G). Because accu- (Supplemental Figure 1G). miR-25 overexpression also alle- mulated renal fibrosis and the collapse of the foot processes are viated the amount of foot process fusion and glomerular base- the main characteristics of glomerulosclerosis, we, therefore, ment membrane (GBM) thickening observed in db/db mice measured immunostaining for glomerulosclerosis marker (Figure1,F,H,andI). PODXL and found that its expression was significantly decreased (Figure 3, D and H). A series of genes related to glomeruloscle- Overexpression of miR-25 Alleviates Secondary rosis displayed a similar decrease compared with in control and Hypertension in Diabetes miRNEG-treated mice (Supplemental Figure 2A). One feature of DN is hypertension. Toexamine if miR-25 could reverse high BP in db/db mice, we first showed that miR-25 Inhibition of miR-25 Activates the Renin-Angiotensin- agomir treatment significantly alleviated hypertension com- Aldosterone System pared with that in untreated db/db mice; however, miRNEG Additionally, we explored whether inhibition of miR-25 could treatment did not (Figure 1J). Because kidney artery resistance accelerate hypertension in wild-type mice. We performed a (KRI) is an important feature of hypertension,22 we color Doppler ultrasound to determine if miR-25 was inhibited performed a color Doppler ultrasound to determine if over- relative to the abnormal KRI. The ultrasound showed that expression of miR-25 was related to the decreased KRI. This miR-25 antagomir treatment significantly increased KRI (Fig- imaging showed that miR-25 agomir significantly reduced ure 4A). Antagomir-25–treated mice displayed high BP compared KRI compared with in db/db andmiRNEG-treatedmice with control and miRNEG mice (Figure 4B). The increased BP (Figure 2A). Alteration of the RAS is a major cause of hyper- corresponded to RAS activation and blood vessel dysfunction tension. To identify if miR-25 agomir treatment decreased detected by immunochemistry (Figure 4, C–E), and levels hypertension by inactivating the RAS, using immunochem- were not changed by miRNEG injection. Similar upregulation istry and ELISA to detect renin, angiotensin I/II, aldosterone, of the RAS was detected by ELISA in the sera from miR-25 and angiotensin 1, we subsequently determined that the RAS antagomir–injected mice compared with control and miRNEG was inhibited as shown by their decreased levels (Figure 2, A mice (Figure 4, F–I). We also detected significantly elevated ex- and B). We also confirmed using vWf immunochemistry that pression changes in a series of genes related to the RAS using overexpression of miR-25 in db/db mice could rescue their qPCR (Supplemental Figure 2B). Oxidant stress is a strong blood vessel structural abnormalities; however, the miRNEG contributor to RAS activation. To rule out whether hyperten- had no effect (Figure 2A). sion caused by miR-25 inhibition is related to oxidant stress, we analyzed several markers of oxidant stress and found sig- Inhibition of miR-25 Causes Proteinuria and Kidney nificant alterations in these markers in miR-25 antagomir– Fibrosis injected mice (Supplemental Figure 2, C–E). However, no Because miR-25 is downregulated in DN, we explored whether such change occurred in miR-25 agomir–treated mice (Sup- inhibition of miR-25 could accelerate kidney fibrosis and plemental Figure 2, C–E). proteinuria in normal mice. Therefore, wild-type (nondia- betic) mice were treated intravenously with 80 mg/kg miR-25 Overexpression of miR-25 Does Not Cause Kidney antagomir or miRNEG antagomir for 3 consecutive days and Injury euthanized attheendof6weeks.Deliveryefficiencies,assessed We also injected the agomir-25 into normal mice to evaluate if by measuring miR-25 expression in the kidneys, showed an this treatment could disturb kidney function. miR-25 expres- approximately sevenfold decrease in kidney miR-25 expres- sion was increased significantly by the treatment, but no sig- sion (Supplemental Figure 1H). We observed that inhibition nificant increase in proteinuria was detected (Figure 5, A and of miR-25 also increased the level of proteinuria and the uri- B). Renal histology of miR-25 agomir–treated mice did not nary albumin-to-creatinine ratio, but miRNEG had no such display any obvious changes in arteriolar thickening, tubular effect (Figure 3, A and B). H&E, PAS, and collagen staining of dilation and atrophy, GBM thickening, or mesangial expan- the kidneys from miR-25 antagomir–treated mice revealed sion (Figure 5C). Only under electron microscopy was a weak increased deposition of fibrillar collagens, mainly in the glo- partial flattening of podocyte foot processes relative to con- meruli, compared with in the control and miRNEG-treated trols visible after miR-25 treatment, but the effect was very mice (Figure 3, C–F). We also analyzed fibrosis-related tran- weak and was not significantly different from that of the miR- scripts by qPCR. In the miR-25 antagomir–treated mice, 25 antagomir–treated group (Figure 5C). Furthermore, on the mRNA expression levels of collagen 1a (I), collagen 4a (IV), ultrasound, the KRI and BP were not increased in agomir-25– Tgf-b1,andFn in the kidneys were significantly increased injected mice compared with controls (Figure 5D). This find- compared with those of controls and miRNEG-treated mice ing is consistent with the expression level of RAS-related genes

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Figure 3. Inhibition of miR-25 resulted in proteinuria and kidney fibrosis in normal mice. (A and B) Quantification of 24-hour albumin excretion and urine albumin-to-creatinine ratio (ACR) in miR-25 antagomir mice. (C and D) Representative images of H&E, PAS, collagen I/IV, TEM, and PODXL staining from kidney sections of miR-25 antagomir–injected mice. Asterisks indicates mesangial expansion, and arrows indicate foot processes in the TEM images. (E and F) Quantification of the collagen I/IV–positive area within the glomeruli. (G) Quantification of GBM thickening after miR-25 antagomir injection. (H) Quantification of the PODXL-positive staining area within the glomeruli. Data are shown as the mean6SEM. Con, control. ***P,0.001.

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Figure 4. Decreased miR-25 cause high blood pressure and activate RAS. (A) Representative image of KRI by color Doppler ultrasound from miR- 25 antagomir–treated mice, with quantification of the KRI in lower right panel. (B) Quantification of the BP from miR-25 antagomir–injected mice. (C–E) Representative images of renin, angiotensin 1 (AT1), and vWf staining of kidney sections from miR-25 antagomir–treated mice; lower right panels represent the quantification of renin-, AT1-, and vWf-positive areas. (F–I) Quantification of the ELISA for serum renin, angiotensin І/П,and aldosterone (ALD) from miR-25 antagomir–injected mice. Data are shown as the mean6SEM. Con, control. *P,0.05; **P,0.01; ***P,0.001.

6 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc–ccc,2017 www.jasn.org BASIC RESEARCH and serum renin, angiotensin І/II, and aldosterone (Figure 5, E targets using the KEGG pathway database and discovered that and F, Supplemental Figure 2B). the Ras signaling pathway was the pathway most significantly altered in miR-25 antagomir–injected mouse kidneys (Sup- miR-25 Target Gene Alteration Is Responsible for plemental Figure 5B). However, miR-25 agomir–treated Disrupted Kidney Function mouse kidneys do not display altered Ras signaling (Supple- miRNAs function as post-transcriptional regulators, mainly by mental Figure 5C). The mRNA levels of these Ras-related affecting the stability of their target mRNAs.23 Toreveal mRNA genes as measured by real-time PCR were significantly down- transcriptomic changes responsible for the kidney impairment regulated in miR-25 antagomir–treated mice but were not observed in mice with miR-25 inhibition and/or overexpression, altered in miR-25 agomir–injected mice (Supplemental Fig- we performed RNA sequencing (RNA-seq) analyses using ure 6, A and B). Furthermore, these same genes were also kidney tissues from wild-type and miR-25 agomir– or antagomir– downregulated in mice with DN, but the effect could be re- treated mice. According to the TargetScan program, the miR- versed by miR-25 overexpression (Supplemental Figure 6C). 25 family is predicted to target 674 mRNAs in the kidney. A miR-25 has also been reported to alleviate oxidant stress in total of 411 mRNAs were significantly dysregulated in miR-25 DN.24 Thus, we assessed some markers of oxidant stress to elu- antagomir–injected mouse kidneys (negative binomial re- cidate whether they compose a part of the mechanism of miR- gression analysis, P,0.05), including 105 upregulated and 25–induced kidney failure. Interestingly, we found that oxidant 306 downregulated mRNAs (Figure 6A, Supplemental Figures stress was significantly activated in miR-25 antagomir–injected 3and4,SupplementalTables1–3, Supplemental Material). By mice but not in miR-25 agomir–treated mice (Supplemental contrast, in miR-25 agomir–injected mice, 228 miR-25 targeted Figure 2, C–E). Most importantly, the overexpression of mRNAs were significantly altered, including 31 upregulated and miR-25 in mice with DN could reverse this oxidant stress 197 downregulated mRNAs (Figure 6B). We hypothesize that (Supplemental Figure 2, F–H). miR-25 caused these alterations by regulating these targeted 674 genes directly or indirectly. To evaluate whether these targeted genes, as a whole, were directly affected by miR-25 DISCUSSION antagomir as primary effects, we randomly selected 674 non- target genes expressed in the kidney and compared the P values In this study, we found that miR-25 was decreased in patients between the target and nontarget genes in the RNA-seq data with DN and diabetic animals or cultured cells exposed to (Figure 6C). Interestingly, the average P value of the 674 elevated glucose. Additional study showed a protective effect target genes was significantly lower than that of the control of miR-25 against DN and DN-induced secondary hyperten- nontarget genes, suggesting that the expression of these direct sion. Diabetic kidneys showed increased extracellular matrix target genes is indeed altered in miR-25 antagomir–injected protein production and RAS activation. However, miR-25 mice, whereas miR-25 agomir–treated mice did not show this agomir injection inhibited such processes in DN and also re- effect (Figure 6D). One gene can be targeted by multiple duced proteinuria in vivo, possibly by inhibiting podocyte miRNAs; thus, the miRNA number is also an important rea- dysfunction and oxidative stress. Notably, inhibition of miR-25 son for regulating gene expression. We also found that the in normal mice resulted in increased kidney fibrosis, podocyte amounts of miR-25 target gene alterations were negatively collapse, proteinuria, and hypertension. By contrast, overex- correlated with the number of miRNA-targeted genes in pression of miR-25 in wild-type mice failed to induce obvious miR-25 antagomir– but not agomir–injected mouse kidneys kidney dysfunction or abnormal BP. Thus, increasing miR-25 (Figure 6, E and F). Todetect whether miR-25 could positively would be advantageous from the therapeutic perspective of regulate its target genes, we performed a luciferase assay, diabetic kidney disease. Additionally, we have shown that which confirmed that inhibition of miR-25 could significantly miR-25 target gene alteration induced by reduction in the repress CDC42 39-UTR luciferase activity and could cause a levels of the miRNA may contribute to disrupted kidney func- mild decrease in RAP1B activity (Figure 6G), whereas we saw tion and that this process may be regulated by the signaling no such repression when we performed similar experiments pathway involving the proto-oncogene Ras. using overexpression of miR-25, which elevated RAP1B activity Oxidative stress contributes to the pathogenesis of DN, and (Figure 6H). Therefore, these results support the hypothesis that thus, antioxidants are used as an adjunctive therapeutic target the kidney failure that results from miR-25 inhibition mainly for diabetic complications.25 In this study, we discovered that originates from direct alteration of miR-25 targets. Todetermine attenuation of miR-25 in normal mice resulted in increased the exact signaling pathway involved in the kidney failure caused production of oxidative stress; however, overexpression of by inhibition of miR-25, we used a bioinformatics approach to miR-25 could reverse this process in db/db mice. In turn, aug- construct a protein network (string-db.org) of miR-25 targets. mentation of miR-25 did not noticeably increase oxidative We discovered that genes in the proto-oncogene Ras signaling stress biosynthesis in normal mice. miR-25 has been reported pathway (Mapk8, Pik3ca/b, Pik3r3, Cdc42,andRap1a/b)wereat to negatively regulate NADPH oxidase 4 (NOX4) in a rat DN the center of this network (www.kegg.jp) (Supplemental Figure model,24 whereas in this study, we observed decreased NOX4 5A). Most interestingly, we analyzed all of the altered miR-25 levels in miR-25 antagomir–treated mice. A debate that centers

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Figure 5. Overexpression of miR-25 does not cause kidney injury in normal mice. (A) miR-25 agomir transfection efficiency in the kidney. (B) Quantification of the 24-hour albumin excretion in miR-25 agomir–treated normal mice. (C) RepresentativeimagesofH&E,PAS,collagenI,and TEM staining from kidney sections of miR-25 agomir–treated normal mice. (D) Representative images of KRI from an miR-25 agomir–treated

8 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc–ccc,2017 www.jasn.org BASIC RESEARCH around NOX4, which is responsible for the production of super- define the gene networks responsible for the critical develop- oxide, is whether the protein might function as a “double-edged mental processes controlled by this miRNA. sword” to confer both protective and detrimental effects.26 Oxidative stress can also promote Ras signaling pathway dysfunction. In this project, we revealed that the kidney failure CONCISE METHODS induced by miR-25 inhibition was related to the Ras signaling pathway. Ras is a member of a family of related G proteins that Serum and Tissue Collection from Human Subjects with are ubiquitously expressed in all cell lineages and organs, and a Diabetes series of studies have confirmed that Ras signaling plays a key This study was approved by the Ethics Review Board of Mudanjiang role in renal fibrosis.27–29 Herein, we found that some Ras Medical University, Heilongjiang, China. Informed consents were signaling–related genes (e.g., Cdc42 and Rap1a/b) and other obtained from all patients. All blood samples and kidney tissues likely miR-25 targets were significantly decreased in miR-25 were collected from patients at the Affiliated Hong Qi Hospital, antagomir–treated mice. However, miR-25 agomir–injected Mudanjiang Medical University from August of 2014 to February of mice do not show this effect. Overexpression of miR-25 in 2017. All samples were transported to the laboratory within 30 diabetic mice could also reverse these gene alterations. Recent minutes after collection. Clinical information from the patients studies have indicated that in vivo podocyte–specific deletion is presented in Supplemental Table 1. of CDC42, a downstream effector of Ras, leads to congenital nephrotic syndrome and glomerulosclerosis.30 In mouse Animal Treatment models, podocyte-specific inactivation of Rap1a and Rap1b The Mudanjiang Medical University Animal Care and Veterinary Ser- induced massive glomerulosclerosis and premature death.31 vices approved all protocols. The investigations conform to the Guide Other studies have also reported a protective role for RAP1 for the Care and Use of Laboratory Animals published by the National against tubular damage in DN, primarily acting to modulate Institutes of Health. Male C57BL/6 mice, weighing 24–26 g (9 weeks), mitochondria-derived oxidative stress.32 Hypertension is a were obtained from the SLAC Laboratory (Shanghai, China). The secondary complication from DN; here, we observed that animals were fed on a standard rodent diet and water ad libitum. miR-25 inhibition led to high BP in normal mice and caused One group of animals (n=5) received weekly intravenous injections severe kidney dysfunction, whereas overexpression of miR-25 by tail vein of 2.5 mg/kg miR-25 agomir (Rabio Co., Guangzhou, could reverse this phenotype. Oxidative stress and Ras signal- China) for 6 weeks, and another group received the same dose of a scram- ing contribute to diabetic secondary hypertension,32 and de- bledcontrolmiRNAinthetailvein(n=5). Normal male C57BL/6 mice creased expression of MAPK8 and Ras-related gene RAP1B were intravenously injected by tail vein with 80 mg/kg miR-25 antagomir are associated with hypertension. In this study, we observed and miRNEG for 3 consecutive days, and two additional injections were that MAPK8 and RAP1B are reduced in miR-25 antagomir– performed for 6 weeks (n=4).36 The animals were euthanized at the end of injected mice with hypertension, and therefore, we speculate 6 weeks after the injections. Male db/db mice (10 weeks; n=5) were ob- that the reversal of hypertension by miR-25 excess may occur tained from the SLAC Laboratory (Shanghai, China), and db/db animals through Ras signaling. On the basis of the RNA-seq results, most received weekly intravenous injections by tail vein of 2.5 mg/kg miR-25 of miR-25’s potential targets in kidney cells in normal mice ap- agomir and miRNEG for 1 month. Type 1 diabetes was induced by in- pear surprisingly to be downregulated not to be upregulated by traperitoneal injections of streptozotocin (in citrate buffer [pH 5.6] by the miRNA. Recently, a new perspective has emerged that the three 70-mg/kg consecutive injections on alternate days; n=5). Diabetes result of miRNA:mRNA targeting is not limited to mRNA de- was defined as a blood glucose level .17 mmol/L on 2 consecutive days, stabilization or inhibition but also, can stabilize and activate and the animals were euthanized after 3 months of diabetes. BP measure- transcription or translation.33–35 Proof of miR-25’s positive reg- ments (RM6240 Biologic Signal Collection and Processing System; ulation of one potential target, CDC42, was shown by changes Chengdu Instrument Factory) and echocardiography (VEVO 2100; in a luciferase reporter induced by inhibition of miR-25 but STTARR, Toronto, Canada) were performed on all of the mice receiving not by its overexpression. Thus, we speculate that inhibition of miR-25 agomir, miR-25 antagomir, or scrambled miRNA before eutha- miR-25 may destabilize its target mRNAs, which in turn, may nasia of the animals. Kidneys, hearts, and serum were collected, and the contribute to kidney dysfunction in normal mice, but the exact majority of the tissues were stored at 280°C. mechanism by which miR-25 reduction promotes kidney dys- function will need to be resolved in the future. Cell Culture Collectively, our findings reveal an essential role of miR-25 Human kidney 2 epithelial cells and human renal glomerular endo- in normal kidney function. Further characterization may re- thelial cells were obtained from ATCC (Shanghai, China). Mouse veal more subtle defects, and detailed molecular analyses will podocytes were purchased from Peking Union Medical College Basic

mouse kidney. The right panel represents quantification of the KRI. (E) Representative images of vWf, renin, and angiotensin 1 (AT1) staining from kidney sections of miR-25 agomir–injected wild-type mice. (F) Quantification of the ELISA for serum renin, angiotensin І/П,and aldosterone (ALD) from miR-25 agomir–injected mice. Data are shown as the mean6SEM. Con, control. ***P,0.001.

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Figure 6. miR-25 positive regulate target gene alteration is responsible for kidney dysfunction. (A and B) Scatterplots representing the alteration of miR-25 target genes from miR-25 antagomir– or agomir–treated mice compared with controls. (C and D) Densitometry of the P values of miRNA target and control genes in the RNA-seq data from miR-25 antagomir– and agomir–injected mice, respectively. (E and F) The correlation between the number of miRNA-targeted mRNAs or agomir-injected mice. (G and H) Luciferase activity in HEK293A cells that were transfected with the indicated 39-UTR reporter constructs showing binding of miR-25 to the 39-UTR of CDC42. Data are shown as the mean6SEM. **P,0.01.

10 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc–ccc,2017 www.jasn.org BASIC RESEARCH

Medical Sciences Cell Resource Center. The cells were serum starved H&E, PAS, and Sirius Red staining, kidney paraffin sections (5 mm) were overnight before all experiments, and the cells were treated with stained using PAS (ScyTek Laboratories Inc., Logan, UT) and Sirius Red normal glucose (5 mmol/L D-glucose), high glucose (25 mmol/L (Abcam) kits according to the manufacturer’sprotocols. D-glucose), or osmotic control (25 mmol/L L-glucose) for 24 hours. ELISA miRNA Extraction and Analysis The mouse blood samples were centrifuged 5000 rpm for 10 minutes, For serum miRNA extraction, samples were centrifuged at 80003g for and the serum was collected. An ELISA for renin, angiotensin 1/2, and 20 minutes, and the supernatants were collected. After adding 750 ml aldosterone was performed using a commercially available kit for TRIzol LS (Invitrogen Life Technologies, Carlsbad, CA) into 250 ml mouse (Abcam; ENZO Life Sciences, Farmingdale, NY) according effusion samples, another 25 ml ath-miR-156a (20 nM; synthesized by to the manufacturer’s instructions. Rabio Co.) was supplemented into each sample tube. Total RNA was extracted using TRIzol LS reagent (Invitrogen Life Technologies) accord- Ultrastructural Analyses ing to the manufacturer’s instructions. The miRNA expression levels were Kidney tissues were fixed in 2.5% glutaraldehyde in 0.1 M phosphate quantifiedbyreal-timePCR.Briefly, miRNAs were reverse transcribed to buffer (pH 7.4) at 4°C for 24 hours. The samples were then washed cDNAwith the MMLVreverse transcription kit (Promega Corp., Madison, with phosphate buffer (0.1 M, pH 7.4) for 12 hours and postfixed for

WI). Subsequently, real-time PCR was performed on an AB7300 (Strata- 20 minutes in 1% OsO4 in 0.1 M phosphate buffer (pH 7.4). The gene, Valencia, CA) using ath-miR-156a as a reference and a mixture of samples were then washed with phosphate buffer (0.1 M, pH 7.4) for RNA extracted from the patient with diabetes as the calibrator. For cell and 30 minutes, dehydrated, and embedded in Epon. Thin sections (50 tissue extraction, miRNAs were extracted from the cells and tissues using nm) were placed on copper grids and stained with 2% uranyl acetate the OMEGA RNA isolation kit (Omega Bio-Tek Inc., Norcross, GA) ac- solution and a 1% solution of lead citrate for 30 minutes. A JEM-1010 cording to the manufacturer’s instructions. Real-time PCR was used with a transmission electron microscope was used to visualize the ultra- final reaction volume of 20 ml containing 9 mlFastStartUniversalSYBR structure. From each specimen, ten randomly selected areas were Green Master Mix (Roche, Beijing, China), 7.4 ml nuclease-free water, 0.8 photographed and analyzed using Image ProPlus software (Image- mlmiRNAprimers(RabioCo.),anda2-ml RT product. The data were Pro Plus; Media Cybernetics, Shanghai, China). normalized to ath-miR-156a or RNU6B small nuclear RNA by a standard curve method to account for differences in reverse transcription efficien- RNA-Seq cies and the amount of template in the reaction mixtures. A total amount of 1.5 mg RNA per sample was used as the input material for the RNA sample preparations. Sequencing libraries mRNA Extraction and RT-PCR were generated using the NEBNext RNA Library Prep Kit for Illumina Total RNA was extracted from cells and tissues using TRIzol (Invitrogen, following the manufacturer’s recommendations (New England BioLabs, Shanghai, China) according to the manufacturer’s instructions. First- Ipswich, MA), and index codes were added to attribute sequences to strand cDNAwas synthesized from 2 mg total RNA using Moloney murine each sample. The clustering of the index-coded samples was performed leukemia virus reverse transcription and a Random Primers kit (Promega on a cBot Cluster Generation System using the HiSEquation 4000 PE Corp.). The ribosomal protein S16 mRNA level served as the internal Cluster Kit (Illumina, San Diego, CA) according to the manufacturer’s control. The primer sequences used are listed in Supplemental Table 2. instructions. After cluster generation, the libraries were sequenced at the Novogene Bioinformatics Institute (Beijing, China) on an Illumina Luciferase Reporter Assay HisEquation 4000 platform, and 150-bp paired end reads were gener- RAS-related gene 39-UTR luciferase vector containing the miR-25 ated. RNA-seq data are available at the Gene Expression Omnibus under response elements was amplified by PCR from mice cDNA. Plasmid accession number GSE83144. DNA (wt-Luc or b-galactosidase control vector) and miR-25 agomir and antagomir were cotransfected into HEK293A cells for 48 hours. Statistical Analyses Luciferase activity was measured using SpectraMax M5 (Molecular De- Data are expressed as the mean6SEM and analyzed using the one-way vices, Sunnyvale, CA) and normalized by measuring b-galactosidase ANOVAand a t test with Dunnett comparison using Prism (version 4; activity. The primers used to generate specific fragments for the mouse GraphPad Software Inc., San Diego, CA). The values were considered RAS-related gene 39-UTR are listed in Supplemental Table 3. significantly different if the P value was ,0.05.

Histology, Immunofluorescence, and Immunohistochemistry ACKNOWLEDGMENTS For immunofluorescence and immunochemistry, mouse mAb against PODXL, actin, collagen I and IV (Abcam, Shanghai, China), renin, angio- This work was supported by, in part, by J Medical University Master tensin 1 (Santa Cruz Biotechnologies Inc., Santa Cruz, CA), vWf (EMD Innovative Research Projects grant 2016YJSCX-22MY (to Y.L.); Millipore, Billerica, MA), and goat polyclonal secondary antibody to mouse Natural Science Foundation of China grants 81070329 (to Y.C.), and rabbit HRP (Abcam) were used. For quantitative morphometry, cells 81770856 (to B.Z.), and 81372951 (to B.Z.); Heilongjiang Province stained in ten randomly selected micrographs were counted using Image Education Fund 1252G065; and Heilongjiang Province Natural Sci- ProPlus software (Image-Pro Plus; Media Cybernetics, Rockville, MD). For ence Foundation grant H201496 (to B.Z.).

J Am Soc Nephrol 28: ccc–ccc, 2017 Inhibition of MicroRNA-25 Causes Kidney Failure 11 BASIC RESEARCH www.jasn.org

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12 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc–ccc,2017 miR-25-agomir-gene-targeted significant eg miRNAnumtargetnum targetsite targetseed regulation yes 319263 11 1 464 8mer downregulation yes 170755 48 3 1637 8mer downregulation no 19335 14 2 4698mer upregulation no 94220 14 1 18187mer-m8 upregulation no 226982 13 1 12067mer-1a upregulation no 23792 16 1 3098mer downregulation no 12912 108 3 4667mer-m8 downregulation no 18711 15 1 26927mer-m8 downregulation no 18627 7 1 17978mer upregulation no 66262 9 1 577mer-1a downregulation no 227449 37 2 2977mer-m8 upregulation no 98396 10 1 2467mer-m8 downregulation no 98415 60 2 45887mer-1a downregulation no 212980 5 1 11227mer-1a downregulation no 13714 5 1 16458mer downregulation no 240753 24 2 21597mer-m8 upregulation yes 329260 62 6 4368 8mer downregulation no 26878 5 1 2357mer-1a downregulation no 240832 9 1 23257mer-m8 downregulation no 11899 18 2 28037mer-m8 upregulation no 98193 7 1 8577mer-1a downregulation no 54418 5 1 14068mer upregulation yes 30928 64 2 2069 7mer-1a downregulation no 226751 11 1 3415 7mer-1a downregulation no 63953 6 1 7548mer upregulation yes 19250 20 1 6614 7mer-1a downregulation yes 66799 15 1 3058mer downregulation no 68187 5 1 1818mer downregulation no 210933 15 1 4607mer-1a downregulation no 213109 12 1 2307mer-1a upregulation yes 17912 12 4 457mer-m8 downregulation no 329154 13 1 2572 8mer downregulation yes 213056 48 2 2567mer-m8 downregulation no 70827 8 1 8517mer-m8 downregulation no 22779 30 1 60908mer downregulation no 18505 16 2 13558mer downregulation yes 14897 19 1 1098 7mer-1a downregulation yes 18627 7 1 17978mer upregulation yes 227399 5 1 5207mer-1a downregulation no 269109 3 1 4417mer-m8 downregulation no 210356 24 3 9777mer-m8 downregulation no 240753 24 2 21597mer-m8 downregulation no 240753 24 2 21597mer-m8 upregulation no 240753 24 2 21597mer-m8 upregulation no 12227 24 2 13408mer upregulation yes 20822 16 1 6177 7mer-1a downregulation yes 74081 28 1 2948 7mer-1a downregulation yes 29809 21 1 48217mer-m8 downregulation no 74106 2 1 2828mer downregulation no 51810 16 1 10337mer-1a upregulation no 67948 28 1 1927mer-1a downregulation no 226778 12 2 1177mer-1a downregulation no 56533 66 2 4078mer downregulation yes 64009 21 1 22248mer upregulation no 16798 22 1 33007mer-1a downregulation yes 20393 84 6 10457mer-1a upregulation no 19272 4 1 5997mer-m8 downregulation no 19714 12 2 4747mer-m8 upregulation no 66686 14 1 2397mer-m8 downregulation no 15166 3 1 3218mer upregulation no 18717 12 2 18418mer downregulation yes 237542 24 2 963 8mer downregulation no 216345 8 1 6807mer-m8 downregulation yes 319468 5 1 43157mer-m8 downregulation no 116848 26 1 11897mer-m8 upregulation no 56535 3 1 7287mer-1a downregulation yes 21412 3 1 2548mer downregulation no 213402 3 1 3447mer-m8 upregulation no 109205 17 1 11347mer-m8 downregulation yes 74747 12 1 8267mer-1a upregulation no 211488 11 1 2854 7mer-1a downregulation no 208666 10 1 22077mer-1a upregulation no 72068 66 3 7777mer-1a downregulation yes 327826 28 1 29787mer-m8 downregulation yes 215449 24 2 11997mer-m8 downregulation yes 71902 17 1 6547mer-m8 downregulation no 15364 28 1 12347mer-1a downregulation no 192678 14 1 1390 8mer downregulation no 117150 7 1 18297mer-1a upregulation no 66701 2 1 1148mer upregulation no 14561 1 1 1378mer downregulation no 22778 18 2 33087mer-1a downregulation no 58172 40 4 30207mer-m8 downregulation no 245944 5 1 3547mer-m8 downregulation no 14025 39 1 3238mer downregulation no 574403 9 1 27107mer-1a downregulation yes 211347 10 1 229 7mer-1a downregulation no 380694 7 1 10908mer downregulation yes 11492 18 1 2068mer downregulation yes 14584 9 1 2508mer downregulation no 66397 5 1 4577mer-1a upregulation yes 93736 36 1 5353 7mer-1a downregulation yes 216742 19 2 2399 8mer downregulation no 14799 18 2 2497mer-1a downregulation no 66771 19 1 25348mer downregulation yes 67128 24 1 1387mer-1a downregulation no 18738 16 1 13778mer downregulation no 68564 74 1 66187mer-m8 upregulation no 360013 3 1 7017mer-m8 upregulation yes 21410 6 1 5107mer-m8 downregulation yes 67468 17 1 3658mer downregulation no 22057 9 1 6568mer downregulation yes 19084 7 1 18047mer-m8 downregulation no 268515 15 1 18788mer upregulation no 209586 2 1 22387mer-1a downregulation no 216551 16 1 22467mer-m8 downregulation no 216558 2 1 2308mer downregulation no 76901 23 1 31047mer-1a downregulation no 15110 7 1 1747mer-m8 downregulation no 11840 8 2 2237mer-1a upregulation no 56697 3 1 11717mer-1a downregulation no 170740 5 1 928mer downregulation no 26398 8 2 5038mer downregulation yes 20317 2 1 827mer-1a downregulation no 18738 16 1 13778mer downregulation no 18099 27 1 15048mer downregulation no 21410 6 1 5107mer-m8 downregulation no 327987 44 1 13017mer-m8 downregulation no 217119 4 1 2838mer downregulation no 268470 20 1 1726 8mer downregulation no 237943 13 1 8717mer-1a downregulation no 353047 13 2 12658mer upregulation no 18195 6 1 14307mer-1a downregulation no 71795 11 1 11537mer-m8 downregulation yes 15081 20 1 3257mer-1a downregulation no 217340 6 1 22697mer-1a downregulation no 72344 4 1 18848mer upregulation no 11302 18 3 10377mer-m8 upregulation yes 75302 19 2 4124 7mer-1a downregulation yes 13435 57 1 1062 8mer downregulation no 104111 18 3 5128mer downregulation no 195733 18 2 6128mer downregulation no 67216 18 2 5117mer-1a downregulation no 17933 124 4 17057mer-m8 downregulation no 72123 16 1 14547mer-1a downregulation no 22160 4 1 6687mer-1a upregulation yes 217463 13 1 2695 8mer downregulation no 15228 26 2 1727mer-m8 downregulation no 18511 9 1 3807mer-m8 downregulation yes 208846 38 2 2416 7mer-1a downregulation yes 15251 5 1 5377mer-1a downregulation no 75627 1 1 4658mer downregulation no 69480 6 1 11698mer downregulation no 12652 2 1 2337mer-1a upregulation no 104859 7 1 13777mer-m8 downregulation no 22031 54 2 4557mer-m8 downregulation no 68520 3 1 1368mer upregulation no 217946 7 1 4737mer-m8 downregulation no 13435 57 1 10628mer upregulation no 208439 24 1 2858mer upregulation no 105005 13 1 18087mer-1a upregulation no 14245 15 3 2908mer upregulation no 20666 35 1 13768mer downregulation no 19088 7 1 5767mer-1a downregulation no 27362 9 1 8778mer downregulation no 664883 77 1 16827mer-m8 upregulation no 94186 36 2 15248mer downregulation no 70611 36 1 13217mer-1a downregulation no 83602 50 2 31767mer-m8 upregulation no 58208 80 2 2348mer upregulation no 11651 6 2 3047mer-m8 upregulation yes 110521 8 1 1057mer-m8 upregulation no 70078 5 1 9077mer-1a upregulation no 16468 69 3 8647mer-m8 downregulation no 218203 11 1 12008mer upregulation no 14057 6 1 15658mer upregulation yes 78521 16 1 37627mer-m8 downregulation yes 105171 20 1 2436 8mer downregulation no 66970 24 2 7287mer-1a downregulation yes 218454 14 2 2510 8mer downregulation no 238871 34 1 29127mer-1a upregulation no 218613 29 1 29147mer-m8 downregulation no 218693 32 2 2677mer-1a upregulation no 94253 14 2 2067mer-1a downregulation yes 13557 23 1 2487mer-m8 downregulation no 56705 14 1 8087mer-1a upregulation yes 20238 198 9 28568mer downregulation no 105239 104 4 22657mer-m8 downregulation no 69046 1 1 13878mer downregulation no 210106 30 2 4468mer downregulation yes 57748 21 2 49037mer-m8 downregulation yes 544963 2 1 5127mer-m8 downregulation no 27015 3 1 1018mer downregulation no 218503 6 1 5927mer-m8 downregulation no 17755 9 1 42378mer downregulation no 328329 13 1 23858mer upregulation no 67295 14 2 55567mer-m8 downregulation yes 14313 7 1 10837mer-m8 downregulation yes 19270 28 1 3935 8mer downregulation no 238988 11 1 13187mer-m8 upregulation no 75901 35 2 33637mer-1a downregulation no 56291 26 1 2757mer-1a downregulation yes 23888 32 2 2484 8mer downregulation no 58245 6 1 388mer downregulation no 223254 9 1 6388mer downregulation no 66480 4 1 1288mer downregulation yes 72993 10 1 4688mer downregulation yes 26419 10 1 1815 8mer downregulation yes 12166 11 1 6287mer-1a downregulation no 1.01E+08 15 1 19237mer-1a downregulation no 105504 9 1 19158mer downregulation no 50523 11 1 3498mer upregulation no 68813 3 1 7728mer downregulation no 18040 6 1 1178mer upregulation no 105513 7 1 8678mer upregulation no 338337 8 1 2688mer downregulation no 211712 12 1 1787 7mer-1a downregulation yes 16597 24 1 1761 7mer-1a downregulation no 105689 7 1 6098mer downregulation no 105445 36 4 1176 8mer downregulation no 238988 11 1 13187mer-m8 upregulation no 17909 7 1 7057mer-m8 upregulation no 15529 11 1 4657mer-m8 downregulation yes 67154 12 1 627mer-1a downregulation no 252973 15 1 6477mer-1a downregulation no 22762 30 1 7257mer-1a downregulation yes 76740 4 1 25127mer-m8 downregulation no 27008 5 1 37507mer-1a upregulation no 239556 7 1 23618mer downregulation no 213988 184 2 847mer-1a downregulation yes 21685 10 2 28098mer upregulation no 12805 9 3 13657mer-m8 downregulation no 11827 3 1 4817mer-1a downregulation no 20273 100 6 11597mer-1a downregulation yes 20683 36 1 1769 7mer-1a downregulation no 15426 17 1 9097mer-1a downregulation no 15423 2 1 7867mer-1a upregulation no 19219 4 2 308mer downregulation yes 68070 12 1 2247 8mer downregulation no 223435 7 1 9097mer-m8 upregulation no 252973 15 1 6477mer-1a downregulation yes 54375 26 2 5427mer-1a downregulation no 69906 2 1 3648mer downregulation no 239420 9 2 17767mer-m8 downregulation no 19357 6 1 2668mer downregulation no 15117 8 1 9407mer-m8 downregulation no 106068 14 2 1376 7mer-1a downregulation no 93686 138 6 567mer-1a downregulation no 17886 10 1 5697mer-m8 downregulation no 223693 6 1 3198mer downregulation no 74158 12 1 1108mer upregulation yes 57259 10 1 23298mer upregulation no 28075 10 1 22067mer-1a downregulation yes 223827 29 1 3908 8mer downregulation no 74775 8 1 3168mer upregulation no 16402 12 1 9478mer downregulation no 268860 20 2 2516 8mer downregulation no 74374 10 2 26677mer-1a downregulation no 20621 16 1 22698mer downregulation no 328643 5 1 2687mer-1a upregulation yes 210126 123 3 109407mer-m8 downregulation yes 22661 63 1 3388 7mer-1a downregulation yes 14314 6 1 1357mer-1a downregulation no 433022 17 1 9817mer-m8 downregulation yes 320712 20 5 1059 7mer-1a downregulation no 19876 8 1 977mer-m8 downregulation no 12013 17 1 32957mer-1a downregulation no 67367 9 1 7937mer-1a upregulation no 338467 3 1 2817mer-m8 downregulation yes 20465 4 1 9368mer upregulation no 71063 4 1 40507mer-m8 downregulation yes 52864 3 1 6448mer upregulation no 545156 31 1 2127mer-m8 downregulation no 14432 6 1 3627mer-m8 downregulation no 208177 7 1 347mer-1a downregulation no 433022 17 1 9817mer-m8 downregulation no 72020 21 1 28357mer-1a downregulation no 239857 46 4 4219 8mer downregulation yes 268902 19 1 727mer-m8 downregulation no 67102 14 1 16998mer downregulation no 104015 30 2 8958mer downregulation no 67367 9 1 7937mer-1a upregulation no 239985 24 2 5158mer downregulation no 68842 24 2 17468mer downregulation no 72536 2 1 1608mer upregulation no 23984 14 1 45918mer downregulation no 240055 11 2 4467mer-m8 downregulation no 224648 10 1 3958 7mer-1a downregulation yes 18519 18 2 1727 8mer downregulation no 17158 18 3 6647mer-m8 upregulation no 78785 10 1 13087mer-1a upregulation yes 67864 4 1 3687mer-m8 downregulation no 106522 5 1 1228mer upregulation no 18754 23 1 16717mer-m8 downregulation no 14236 17 1 26078mer downregulation no 380608 2 1 1608mer upregulation yes 19317 120 1 20697mer-1a downregulation no 65962 10 2 4337mer-1a upregulation no 58226 10 2 7177mer-1a upregulation yes 17691 23 1 7538mer upregulation yes 12488 18 1 31007mer-m8 downregulation no 210982 19 1 2902 7mer-1a downregulation no 110332 1 1 3408mer upregulation no 21815 35 5 3048mer upregulation yes 268980 7 1 5747mer-1a downregulation no 72536 2 1 1608mer downregulation no 381157 27 1 1640 8mer downregulation no 14465 8 1 6557mer-m8 downregulation no 67393 4 1 387mer-m8 upregulation no 225432 9 1 29367mer-1a downregulation yes 240283 13 1 1562 8mer downregulation no 107022 6 1 1858mer downregulation no 70417 4 1 33887mer-1a downregulation yes 20496 13 1 2731 7mer-1a downregulation no 52662 8 1 9897mer-1a downregulation no 21413 86 2 4347mer-1a downregulation no 17131 14 1 13777mer-m8 upregulation yes 16573 6 1 1887mer-m8 downregulation no 18145 5 1 9757mer-1a downregulation no 225207 12 1 5657mer-1a downregulation no 13506 2 1 5098mer downregulation no 225266 5 2 17147mer-m8 downregulation no 28105 20 2 17808mer upregulation no 14119 13 1 16127mer-1a downregulation yes 54670 9 1 22408mer downregulation no 13176 22 1 51507mer-1a upregulation no 212163 12 1 6377mer-1a downregulation no 72056 2 1 797mer-m8 upregulation no 225888 88 4 1777mer-m8 downregulation yes 12660 6 1 2338mer upregulation no 14682 13 2 19597mer-m8 downregulation yes 72351 2 1 348mer downregulation no 20510 13 1 5507mer-1a upregulation yes 226089 12 2 1574 8mer downregulation no 19211 57 1 28608mer downregulation yes 209478 10 1 263 7mer-1a downregulation no 18648 3 1 8788mer upregulation no 18089 3 1 8338mer downregulation no 20170 1 1 628mer upregulation yes 226252 10 1 2346 8mer downregulation no 56613 7 1 4347mer-m8 upregulation no 208922 41 5 2946 8mer downregulation no 14218 62 4 47157mer-m8 downregulation yes 107368 8 1 2162 8mer downregulation yes 74998 31 2 3546 7mer-1a downregulation no 108909 4 1 2617mer-m8 downregulation no 338366 6 1 2328mer downregulation yes 209645 6 2 17607mer-m8 downregulation no 353282 16 2 3751 8mer downregulation no 241263 11 1 2828 7mer-1a downregulation no 56876 15 5 3207mer-m8 upregulation no 18128 8 1 15877mer-1a upregulation no 64930 20 1 2848mer downregulation yes 227723 20 2 2328 8mer downregulation yes 26360 9 1 14037mer-1a downregulation no 69601 24 3 27137mer-m8 downregulation no 227867 28 1 8687mer-1a downregulation no 227960 3 1 22717mer-m8 downregulation yes 16403 5 1 6388mer downregulation no 65964 11 1 51137mer-1a downregulation no 70599 3 1 3988mer downregulation no 241514 3 1 4127mer-1a downregulation yes 16410 3 1 30808mer downregulation no 381379 2 1 2457mer-m8 upregulation no 55935 9 1 3497mer-m8 upregulation no 11695 8 1 37557mer-1a upregulation yes 16909 8 4 3527mer-m8 downregulation yes 12125 90 6 28457mer-m8 downregulation yes 94249 7 1 448mer downregulation no 433485 6 1 3708mer downregulation no 14225 9 1 10737mer-1a upregulation yes 16569 10 1 16537mer-m8 downregulation no 22348 4 1 5957mer-m8 downregulation no 21969 14 1 3817mer-1a downregulation no 76080 12 2 5567mer-1a downregulation no 57138 16 3 22287mer-1a upregulation no 17979 12 1 6167mer-1a upregulation no 67017 7 1 5787mer-1a downregulation yes 241226 11 1 1402 8mer downregulation yes 67991 48 2 3801 7mer-1a downregulation no 18128 8 1 15877mer-1a downregulation no 241311 42 1 4562 7mer-1a downregulation yes 68365 10 1 1914 8mer downregulation no 76899 11 1 18708mer downregulation yes 24136 39 1 8657mer-m8 downregulation yes 407823 21 1 335 8mer downregulation no 20269 17 1 19297mer-m8 downregulation no 53416 14 1 10847mer-m8 downregulation no 241494 18 3 1008 7mer-1a downregulation no 228136 13 1 2607mer-m8 downregulation yes 19271 18 1 1005 8mer downregulation yes 15259 90 8 9007mer-1a downregulation yes 99003 19 1 4697mer-m8 downregulation no 211499 15 3 5797mer-m8 upregulation yes 14118 11 1 8098mer downregulation no 12848 19 1 3807mer-1a downregulation no 215653 10 1 25087mer-m8 downregulation no 81910 4 1 2957mer-m8 upregulation no 329540 66 2 1248 8mer downregulation yes 66680 5 1 1127mer-1a upregulation no 65112 16 1 3827mer-1a downregulation no 269401 11 1 2118mer upregulation no 80892 50 1 19807mer-m8 upregulation no 81004 23 1 23478mer upregulation no 18417 4 1 9888mer downregulation no 18706 22 1 16518mer downregulation yes 67120 7 1 6617mer-1a downregulation yes 229227 2 1 2528mer downregulation no 73333 2 1 1107mer-1a downregulation yes 269424 88 4 2847 7mer-1a downregulation no 18526 33 1 3617mer-1a downregulation yes 74838 29 1 1208 7mer-1a downregulation no 50754 87 6 16308mer upregulation no 229541 4 1 6718mer downregulation no 17210 8 1 98mer upregulation no 66471 5 1 17597mer-m8 downregulation no 108097 4 1 29367mer-1a downregulation no 18072 17 1 15487mer-1a downregulation yes 229675 19 1 1377 8mer downregulation no 13171 4 1 4727mer-m8 downregulation yes 214137 6 1 2947mer-m8 downregulation no 51886 23 1 20987mer-m8 downregulation yes 320840 18 1 378 7mer-1a downregulation yes 74252 10 2 797mer-m8 downregulation yes 72007 29 2 16577mer-m8 downregulation no 329679 19 1 33838mer upregulation yes 60596 4 1 8317mer-1a downregulation no 70762 10 5 12167mer-1a upregulation no 53814 1 1 1107mer-m8 downregulation no 109905 12 1 2247mer-1a downregulation no 99738 9 1 8928mer downregulation no 229709 6 1 19277mer-1a downregulation yes 13609 13 1 12387mer-m8 upregulation no 74442 26 1 35657mer-1a downregulation yes 114249 4 2 1547mer-m8 downregulation no 214133 25 1 22098mer upregulation no 242297 2 1 1157mer-m8 downregulation no 12448 14 2 4927mer-m8 downregulation no 12395 150 3 35058mer downregulation no 17389 20 1 6817mer-1a downregulation no 51813 2 1 6208mer downregulation no 66625 9 1 13708mer upregulation no 67727 10 1 47377mer-1a downregulation yes 209131 30 1 8607mer-m8 downregulation no 50780 6 1 5178mer upregulation yes 373864 9 1 3728mer upregulation no 77739 8 1 18488mer downregulation no 18027 210 6 9467mer-m8 upregulation no 72475 18 2 1537mer-1a upregulation yes 18710 16 2 3202 7mer-1a downregulation no 14201 2 1 6197mer-1a upregulation no 100383 8 1 12388mer upregulation yes 20970 6 1 24407mer-m8 downregulation no 20544 4 1 11548mer downregulation yes 269593 21 1 2570 8mer downregulation yes 69743 22 1 8557mer-m8 downregulation no 67087 22 2 5607mer-1a downregulation no 70673 50 2 46417mer-1a downregulation yes 56036 4 1 5797mer-m8 upregulation no 18201 3 1 707mer-m8 upregulation no 230025 3 1 7037mer-m8 downregulation no 66625 9 1 13708mer upregulation no 73469 66 4 32927mer-m8 downregulation no 230125 5 1 29087mer-m8 downregulation yes 107684 10 2 20277mer-m8 upregulation no 16600 17 1 7518mer upregulation yes 19266 58 2 1275 8mer downregulation no 18028 246 6 18627mer-1a upregulation yes 68268 16 1 7467mer-1a downregulation yes 108079 16 1 51167mer-m8 downregulation no 106564 2 1 4028mer upregulation no 83557 21 1 15757mer-1a downregulation no 27224 7 1 19347mer-m8 downregulation no 13842 13 1 13357mer-1a downregulation yes 230848 3 1 10017mer-m8 upregulation no 12540 4 1 977mer-1a downregulation no 69743 22 1 8557mer-m8 upregulation no 70673 50 2 46417mer-1a downregulation no 20481 28 1 15927mer-m8 downregulation no 20346 45 3 637mer-1a downregulation yes 231070 13 1 9447mer-m8 downregulation no 13799 21 1 577mer-1a upregulation no 16527 8 1 22847mer-1a downregulation no 14284 26 1 5978mer downregulation yes 19822 4 1 6228mer downregulation no 231207 98 4 10287mer-m8 downregulation yes 19664 45 6 6947mer-1a downregulation no 67249 8 1 2867mer-1a downregulation yes 54216 8 1 12628mer downregulation yes 77569 20 1 3448mer downregulation no 320827 13 2 25647mer-m8 upregulation no 15891 3 1 898mer downregulation no 231549 8 2 5058mer downregulation yes 17765 17 1 1711 7mer-1a downregulation yes 69587 16 1 2610 8mer downregulation no 209683 9 1 4767mer-1a downregulation no 21386 12 2 8617mer-1a downregulation no 93897 1 1 6708mer downregulation no 140904 16 2 2357mer-1a upregulation no 66114 1 1 4038mer upregulation no 74198 6 1 3577mer-1a upregulation no 80752 2 1 6828mer upregulation no 77053 6 1 11497mer-m8 downregulation no 17135 8 1 21067mer-1a upregulation no 320365 4 1 3557mer-m8 upregulation yes 100710 12 1 2233 8mer downregulation yes 70797 18 2 9277mer-m8 downregulation no 68770 13 1 1277mer-m8 downregulation no 20817 21 1 12897mer-1a downregulation no 18196 6 1 1087mer-m8 downregulation no 245945 57 6 17428mer upregulation no 243043 10 1 4387mer-1a downregulation no 67980 6 1 567mer-1a downregulation yes 72313 10 1 3167mer-1a upregulation yes 23881 65 10 3957mer-m8 downregulation yes 231506 4 2 17177mer-m8 downregulation yes 14020 15 1 2988mer downregulation no 12889 4 1 12647mer-1a downregulation no 26431 30 3 27487mer-1a upregulation no 252972 10 1 297mer-1a downregulation no 11938 14 1 5968mer downregulation no 19679 12 1 16548mer upregulation no 243272 27 2 5306 7mer-1a downregulation no 75788 34 2 28357mer-1a upregulation no 243362 36 2 12947mer-m8 downregulation yes 12843 9 1 1728mer downregulation no 243725 20 1 5886 7mer-1a downregulation no 114142 102 2 7307mer-m8 downregulation no 16508 6 1 7427mer-1a downregulation no 18181 12 2 647mer-m8 downregulation yes 76788 16 1 2390 8mer downregulation yes 109624 8 1 2188 7mer-1a downregulation no 243764 2 1 1117mer-m8 downregulation no 78937 18 1 40998mer downregulation yes 14461 7 1 12888mer upregulation no 23945 18 3 3627mer-1a downregulation no 320265 7 1 6248mer downregulation no 17342 54 3 14917mer-1a downregulation no 16438 4 1 3598mer downregulation no 192193 12 1 3604 8mer downregulation no 108073 6 1 8747mer-1a downregulation no 72895 7 1 2817mer-m8 upregulation no 232333 25 2 12377mer-1a upregulation no 20965 14 2 22088mer upregulation no 71779 10 1 17817mer-m8 downregulation no 67602 5 1 15208mer downregulation no 19277 16 4 3258mer downregulation no 64450 8 1 1407mer-1a downregulation no 73178 13 1 1468mer downregulation no 319832 6 1 7348mer downregulation no 192198 11 1 287mer-1a downregulation no 83922 7 2 22047mer-m8 downregulation yes 208647 2 1 5477mer-m8 downregulation no 109880 38 2 5896 8mer downregulation no 243547 7 1 15787mer-1a upregulation no 108655 87 3 47087mer-1a upregulation no 330401 25 1 1527mer-1a upregulation no 12288 56 4 12547mer-1a downregulation no 14789 1 1 5518mer upregulation no 16485 28 1 14928mer downregulation no 12515 6 2 7148mer upregulation no 13860 14 1 12947mer-1a upregulation no 67456 5 1 658mer downregulation no 71722 30 3 5508mer downregulation no 170742 3 1 4288mer upregulation no 12606 14 1 9467mer-m8 upregulation no 52428 8 1 11668mer downregulation no 12036 12 3 868mer upregulation no 140919 5 1 1777mer-m8 downregulation yes 15204 3 1 3068mer downregulation no 233406 2 1 6877mer-m8 downregulation no 116904 5 1 12557mer-1a upregulation no 269959 12 1 1680 8mer downregulation yes 50490 8 2 397mer-m8 downregulation no 22141 15 1 40957mer-m8 upregulation no 11535 6 1 2897mer-m8 upregulation yes 21676 117 6 79467mer-m8 downregulation no 233812 26 2 26007mer-m8 upregulation no 19647 10 1 3127mer-1a upregulation no 104175 10 1 1470 7mer-1a downregulation yes 57752 18 3 338mer upregulation yes 101476 5 1 1181 8mer downregulation no 15373 2 1 1627mer-m8 upregulation yes 232807 5 1 4318mer upregulation no 12315 8 1 10437mer-1a upregulation no 67224 2 1 5917mer-m8 upregulation yes 56632 21 3 4167mer-1a upregulation no 66412 10 1 11428mer downregulation yes 12877 12 1 3757mer-1a upregulation no 1.01E+08 3 1 13987mer-1a upregulation yes 13690 48 4 3897mer-1a downregulation yes 50781 6 1 308mer downregulation no 21676 117 6 79467mer-m8 upregulation yes 319622 12 1 5367mer-m8 downregulation no 18020 4 1 8418mer downregulation no 627214 17 1 19337mer-m8 upregulation no 57754 3 1 7647mer-1a downregulation no 12577 8 2 1587mer-m8 upregulation yes 68904 34 2 3598 7mer-1a downregulation yes 78560 13 1 1255 7mer-1a downregulation no 52065 17 1 5128mer downregulation no 234267 10 1 5647mer-m8 downregulation no 15111 6 1 1187mer-m8 upregulation yes 16598 2 1 2148mer upregulation no 622675 22 1 3341 8mer downregulation no 73945 16 1 28558mer downregulation no 19724 6 1 4637mer-m8 upregulation no 382030 5 1 1258mer upregulation yes 214627 48 3 307mer-m8 downregulation no 109151 22 1 2378 7mer-1a downregulation no 19651 5 1 6727mer-m8 downregulation no 68051 9 2 14227mer-1a upregulation no 66369 2 1 2708mer upregulation no 15118 16 1 277mer-m8 upregulation no 54446 104 2 67377mer-m8 downregulation no 66894 3 1 15878mer downregulation no 11906 27 1 29207mer-m8 upregulation yes 244650 23 2 35897mer-m8 downregulation no 234734 2 1 3588mer upregulation no 93742 7 1 327mer-1a upregulation no 94109 17 1 26727mer-1a upregulation no 54384 1 1 597mer-m8 upregulation no 102141 3 1 3727mer-m8 downregulation no 69260 7 1 887mer-1a downregulation no 382014 7 1 3437mer-1a upregulation no 15245 19 1 4127mer-m8 downregulation yes 52335 26 1 3758 7mer-1a downregulation no 12398 63 3 18048mer downregulation no 93742 7 1 327mer-1a upregulation no 72826 13 1 2827mer-1a downregulation yes 75747 1 1 2177mer-m8 downregulation no 67398 8 1 8738mer downregulation no 58235 16 1 28778mer upregulation no 114873 3 1 5268mer downregulation no 235323 4 1 9348mer downregulation no 20320 11 1 9727mer-m8 downregulation no 71973 7 1 9267mer-m8 upregulation yes 11487 20 2 5097mer-1a downregulation no 319758 19 1 2616 7mer-1a downregulation no 59046 44 2 33397mer-1a upregulation no 17918 12 1 14098mer downregulation yes 76477 1 1 3378mer downregulation yes 211586 96 6 8607mer-m8 downregulation no 13813 6 2 1137mer-m8 upregulation no 54214 2 1 3548mer downregulation no 57246 9 1 45288mer downregulation no 80517 4 1 637mer-m8 downregulation no 235283 1 1 348mer upregulation yes 72828 2 1 9368mer downregulation yes 20660 2 1 897mer-1a downregulation no 192663 7 1 6677mer-1a downregulation no 330941 16 1 2630 7mer-1a downregulation yes 244895 22 1 12627mer-m8 downregulation no 93683 19 1 25367mer-1a downregulation no 207667 36 4 4057mer-m8 upregulation no 17130 6 1 1997mer-m8 upregulation yes 235442 18 1 3103 8mer downregulation no 83603 6 2 12378mer downregulation yes 108837 2 1 9998mer downregulation no 20616 8 1 13847mer-1a downregulation yes 192287 6 1 12967mer-m8 downregulation yes 74769 3 1 10808mer downregulation no 108068 2 1 877mer-1a downregulation no 12217 23 1 38297mer-m8 upregulation no 270201 12 1 18127mer-m8 upregulation no 69035 9 1 13087mer-1a downregulation yes 13205 41 1 1438 8mer downregulation no 18555 8 2 5647mer-1a upregulation no 74365 16 1 767mer-1a downregulation yes 53623 14 1 1217mer-m8 downregulation yes 14265 21 1 1739 8mer downregulation no 12111 2 1 11308mer downregulation no 236899 24 2 9467mer-1a upregulation yes 11977 34 2 3150 8mer downregulation no 245595 9 1 8907mer-m8 downregulation no 67117 4 1 1108mer downregulation yes 12361 36 1 10287mer-m8 downregulation no 72018 2 1 4447mer-1a downregulation yes 14396 3 1 19277mer-m8 downregulation no 17524 4 1 3288mer upregulation yes 22589 11 1 5748mer downregulation no 13193 124 4 59087mer-1a downregulation no 70771 3 1 6057mer-m8 upregulation yes 26900 18 1 1260 8mer downregulation miR-25-antagomir-gene-targeted significant eg miRNAnumtargetnum targetsite targetseed regulation yes 319263 11 1 464 8mer downregulation yes 170755 48 3 1637 8mer downregulation yes 94220 14 1 18187mer-m8 upregulation yes 226982 13 1 12067mer-1a upregulation yes 12912 108 3 4667mer-m8 downregulation yes 66262 9 1 577mer-1a downregulation yes 98396 10 1 2467mer-m8 downregulation yes 212980 5 1 1122 7mer-1a downregulation yes 329260 62 6 4368 8mer downregulation yes 240832 9 1 23257mer-m8 downregulation

yes 30928 64 2 2069 7mer-1a downregulation yes 19250 20 1 6614 7mer-1a downregulation yes 66799 15 1 3058mer downregulation yes 68187 5 1 1818mer downregulation yes 213109 12 1 230 7mer-1a downregulation yes 17912 12 4 457mer-m8 downregulation yes 329154 13 1 2572 8mer downregulation yes 213056 48 2 2567mer-m8 downregulation yes 70827 8 1 8517mer-m8 downregulation yes 14897 19 1 1098 7mer-1a downregulation yes 18627 7 1 17978mer upregulation yes 227399 5 1 5207mer-1a downregulation

yes 12227 24 2 13408mer upregulation yes 20822 16 1 6177 7mer-1a downregulation yes 74081 28 1 2948 7mer-1a downregulation yes 29809 21 1 48217mer-m8 downregulation yes 74106 2 1 2828mer downregulation yes 51810 16 1 1033 7mer-1a downregulation yes 67948 28 1 1927mer-1a downregulation yes 226778 12 2 117 7mer-1a downregulation yes 64009 21 1 22248mer upregulation yes 16798 22 1 3300 7mer-1a downregulation yes 20393 84 6 10457mer-1a upregulation yes 19272 4 1 5997mer-m8 downregulation

yes 18717 12 2 18418mer upregulation yes 237542 24 2 963 8mer downregulation yes 319468 5 1 43157mer-m8 downregulation yes 56535 3 1 7287mer-1a downregulation yes 21412 3 1 2548mer downregulation yes 74747 12 1 8267mer-1a upregulation yes 211488 11 1 2854 7mer-1a downregulation yes 72068 66 3 7777mer-1a downregulation yes 327826 28 1 29787mer-m8 downregulation yes 215449 24 2 11997mer-m8 downregulation yes 71902 17 1 6547mer-m8 downregulation yes 192678 14 1 1390 8mer downregulation yes 14561 1 1 1378mer downregulation yes 58172 40 4 30207mer-m8 downregulation yes 245944 5 1 3547mer-m8 downregulation yes 211347 10 1 229 7mer-1a downregulation yes 11492 18 1 2068mer downregulation yes 14584 9 1 2508mer downregulation yes 66397 5 1 4577mer-1a downregulation yes 93736 36 1 5353 7mer-1a downregulation yes 216742 19 2 2399 8mer downregulation yes 66771 19 1 2534 8mer downregulation yes 67128 24 1 1387mer-1a downregulation yes 18738 16 1 1377 8mer downregulation yes 68564 74 1 66187mer-m8 downregulation yes 360013 3 1 7017mer-m8 upregulation yes 67468 17 1 3658mer downregulation yes 22057 9 1 6568mer upregulation yes 19084 7 1 18047mer-m8 downregulation yes 268515 15 1 1878 8mer upregulation yes 216551 16 1 22467mer-m8 downregulation yes 216558 2 1 2308mer downregulation

yes 56697 3 1 11717mer-1a downregulation yes 170740 5 1 928mer downregulation yes 26398 8 2 5038mer downregulation yes 20317 2 1 827mer-1a downregulation yes 18099 27 1 1504 8mer downregulation yes 327987 44 1 13017mer-m8 downregulation yes 268470 20 1 1726 8mer downregulation yes 237943 13 1 871 7mer-1a downregulation

yes 72344 4 1 18848mer upregulation yes 75302 19 2 4124 7mer-1a downregulation yes 13435 57 1 1062 8mer downregulation yes 67216 18 2 5117mer-1a downregulation yes 72123 16 1 1454 7mer-1a downregulation yes 217463 13 1 2695 8mer downregulation yes 208846 38 2 2416 7mer-1a downregulation yes 15251 5 1 5377mer-1a downregulation yes 75627 1 1 4658mer downregulation

yes 22031 54 2 4557mer-m8 downregulation yes 217946 7 1 4737mer-m8 downregulation yes 105005 13 1 1808 7mer-1a downregulation yes 14245 15 3 2908mer upregulation yes 27362 9 1 8778mer downregulation yes 664883 77 1 16827mer-m8 upregulation yes 83602 50 2 31767mer-m8 downregulation yes 58208 80 2 2348mer upregulation yes 11651 6 2 3047mer-m8 upregulation yes 110521 8 1 1057mer-m8 upregulation yes 70078 5 1 9077mer-1a downregulation yes 218203 11 1 1200 8mer downregulation yes 78521 16 1 37627mer-m8 downregulation yes 105171 20 1 2436 8mer downregulation yes 218454 14 2 2510 8mer downregulation yes 238871 34 1 29127mer-1a upregulation yes 218613 29 1 29147mer-m8 downregulation yes 218693 32 2 267 7mer-1a downregulation yes 13557 23 1 2487mer-m8 downregulation yes 56705 14 1 8087mer-1a downregulation yes 20238 198 9 28568mer downregulation yes 105239 104 4 22657mer-m8 downregulation yes 69046 1 1 13878mer downregulation yes 210106 30 2 446 8mer downregulation yes 57748 21 2 49037mer-m8 downregulation yes 544963 2 1 5127mer-m8 downregulation yes 27015 3 1 1018mer downregulation yes 218503 6 1 5927mer-m8 downregulation

yes 14313 7 1 10837mer-m8 downregulation yes 19270 28 1 3935 8mer downregulation yes 56291 26 1 2757mer-1a downregulation yes 23888 32 2 2484 8mer downregulation

yes 72993 10 1 4688mer downregulation yes 26419 10 1 1815 8mer downregulation yes 12166 11 1 6287mer-1a downregulation yes 50523 11 1 3498mer downregulation

yes 338337 8 1 2688mer downregulation yes 16597 24 1 1761 7mer-1a downregulation yes 105689 7 1 6098mer upregulation yes 105445 36 4 1176 8mer downregulation yes 17909 7 1 7057mer-m8 downregulation yes 15529 11 1 4657mer-m8 downregulation yes 252973 15 1 647 7mer-1a downregulation

yes 21685 10 2 28098mer upregulation

yes 20683 36 1 1769 7mer-1a downregulation yes 15426 17 1 9097mer-1a upregulation yes 15423 2 1 7867mer-1a upregulation yes 68070 12 1 2247 8mer downregulation yes 223435 7 1 9097mer-m8 downregulation yes 54375 26 2 5427mer-1a downregulation yes 19357 6 1 2668mer downregulation yes 106068 14 2 1376 7mer-1a downregulation yes 93686 138 6 567mer-1a downregulation yes 17886 10 1 5697mer-m8 downregulation yes 57259 10 1 23298mer upregulation yes 28075 10 1 22067mer-1a upregulation yes 223827 29 1 3908 8mer downregulation yes 74775 8 1 3168mer upregulation yes 268860 20 2 2516 8mer downregulation yes 20621 16 1 2269 8mer downregulation yes 210126 123 3 109407mer-m8 downregulation yes 22661 63 1 3388 7mer-1a downregulation yes 14314 6 1 1357mer-1a downregulation yes 433022 17 1 9817mer-m8 downregulation yes 320712 20 5 1059 7mer-1a downregulation yes 12013 17 1 3295 7mer-1a downregulation yes 338467 3 1 2817mer-m8 downregulation yes 20465 4 1 9368mer downregulation yes 71063 4 1 40507mer-m8 downregulation yes 52864 3 1 6448mer upregulation yes 545156 31 1 2127mer-m8 downregulation yes 208177 7 1 347mer-1a downregulation yes 72020 21 1 2835 7mer-1a downregulation yes 268902 19 1 727mer-m8 downregulation yes 67367 9 1 7937mer-1a upregulation

yes 240055 11 2 4467mer-m8 downregulation yes 224648 10 1 3958 7mer-1a downregulation yes 18519 18 2 1727 8mer downregulation yes 17158 18 3 6647mer-m8 downregulation yes 78785 10 1 13087mer-1a upregulation yes 67864 4 1 3687mer-m8 downregulation yes 106522 5 1 1228mer upregulation yes 14236 17 1 2607 8mer downregulation yes 380608 2 1 1608mer upregulation yes 19317 120 1 20697mer-1a downregulation yes 65962 10 2 4337mer-1a upregulation yes 17691 23 1 7538mer upregulation yes 12488 18 1 31007mer-m8 downregulation yes 210982 19 1 2902 7mer-1a downregulation yes 21815 35 5 3048mer upregulation yes 268980 7 1 5747mer-1a downregulation

yes 225432 9 1 2936 7mer-1a downregulation yes 240283 13 1 1562 8mer downregulation yes 107022 6 1 1858mer downregulation yes 20496 13 1 2731 7mer-1a downregulation yes 17131 14 1 13777mer-m8 downregulation yes 16573 6 1 1887mer-m8 downregulation yes 18145 5 1 9757mer-1a downregulation yes 225266 5 2 17147mer-m8 downregulation yes 54670 9 1 22408mer downregulation yes 212163 12 1 637 7mer-1a downregulation yes 72056 2 1 797mer-m8 upregulation yes 225888 88 4 1777mer-m8 downregulation yes 12660 6 1 2338mer upregulation yes 14682 13 2 19597mer-m8 upregulation yes 72351 2 1 348mer downregulation yes 226089 12 2 1574 8mer downregulation yes 19211 57 1 2860 8mer downregulation yes 209478 10 1 263 7mer-1a downregulation yes 20170 1 1 628mer upregulation yes 226252 10 1 2346 8mer downregulation yes 56613 7 1 4347mer-m8 upregulation yes 14218 62 4 47157mer-m8 downregulation yes 107368 8 1 2162 8mer downregulation yes 74998 31 2 3546 7mer-1a downregulation yes 209645 6 2 17607mer-m8 downregulation yes 56876 15 5 3207mer-m8 upregulation yes 227723 20 2 2328 8mer downregulation yes 26360 9 1 14037mer-1a downregulation yes 227867 28 1 868 7mer-1a downregulation yes 227960 3 1 22717mer-m8 downregulation yes 16403 5 1 6388mer downregulation yes 70599 3 1 3988mer downregulation yes 16410 3 1 30808mer downregulation yes 55935 9 1 3497mer-m8 upregulation yes 16909 8 4 3527mer-m8 downregulation yes 12125 90 6 28457mer-m8 downregulation

yes 16569 10 1 16537mer-m8 downregulation yes 67017 7 1 5787mer-1a downregulation yes 241226 11 1 1402 8mer downregulation yes 241311 42 1 4562 7mer-1a downregulation yes 68365 10 1 1914 8mer downregulation yes 76899 11 1 1870 8mer downregulation yes 24136 39 1 8657mer-m8 downregulation yes 53416 14 1 10847mer-m8 downregulation yes 241494 18 3 1008 7mer-1a downregulation yes 228136 13 1 2607mer-m8 downregulation yes 19271 18 1 1005 8mer downregulation yes 15259 90 8 9007mer-1a downregulation yes 99003 19 1 4697mer-m8 downregulation yes 14118 11 1 8098mer downregulation yes 12848 19 1 3807mer-1a downregulation yes 81910 4 1 2957mer-m8 upregulation yes 66680 5 1 1127mer-1a upregulation yes 65112 16 1 3827mer-1a upregulation yes 269401 11 1 2118mer upregulation yes 81004 23 1 2347 8mer downregulation yes 67120 7 1 6617mer-1a downregulation yes 229227 2 1 2528mer downregulation yes 269424 88 4 2847 7mer-1a downregulation yes 50754 87 6 16308mer upregulation yes 66471 5 1 17597mer-m8 downregulation

yes 13171 4 1 4727mer-m8 downregulation yes 214137 6 1 2947mer-m8 downregulation yes 51886 23 1 20987mer-m8 downregulation yes 320840 18 1 378 7mer-1a downregulation yes 74252 10 2 797mer-m8 downregulation yes 72007 29 2 16577mer-m8 downregulation yes 60596 4 1 8317mer-1a downregulation yes 109905 12 1 224 7mer-1a downregulation yes 229709 6 1 1927 7mer-1a downregulation yes 74442 26 1 3565 7mer-1a downregulation yes 114249 4 2 1547mer-m8 downregulation yes 214133 25 1 2209 8mer upregulation

yes 51813 2 1 6208mer downregulation yes 66625 9 1 13708mer upregulation yes 67727 10 1 4737 7mer-1a downregulation yes 209131 30 1 8607mer-m8 downregulation yes 373864 9 1 3728mer upregulation yes 77739 8 1 18488mer downregulation yes 18027 210 6 9467mer-m8 upregulation yes 72475 18 2 1537mer-1a upregulation yes 18710 16 2 3202 7mer-1a downregulation yes 14201 2 1 6197mer-1a upregulation yes 20970 6 1 24407mer-m8 downregulation yes 269593 21 1 2570 8mer downregulation yes 67087 22 2 5607mer-1a upregulation yes 70673 50 2 4641 7mer-1a downregulation yes 56036 4 1 5797mer-m8 upregulation

yes 73469 66 4 32927mer-m8 downregulation yes 107684 10 2 20277mer-m8 upregulation yes 16600 17 1 7518mer upregulation yes 19266 58 2 12758mer upregulation yes 18028 246 6 18627mer-1a upregulation yes 68268 16 1 7467mer-1a downregulation yes 108079 16 1 51167mer-m8 downregulation yes 27224 7 1 19347mer-m8 downregulation yes 230848 3 1 10017mer-m8 upregulation yes 12540 4 1 977mer-1a downregulation

yes 231070 13 1 9447mer-m8 upregulation yes 16527 8 1 22847mer-1a upregulation yes 14284 26 1 5978mer upregulation yes 19822 4 1 6228mer downregulation yes 231207 98 4 10287mer-m8 downregulation yes 19664 45 6 6947mer-1a downregulation yes 54216 8 1 12628mer downregulation

yes 231549 8 2 5058mer downregulation yes 69587 16 1 2610 8mer downregulation yes 209683 9 1 4767mer-1a upregulation

yes 66114 1 1 4038mer upregulation yes 74198 6 1 3577mer-1a upregulation yes 77053 6 1 11497mer-m8 downregulation yes 17135 8 1 21067mer-1a upregulation yes 100710 12 1 2233 8mer downregulation yes 70797 18 2 9277mer-m8 downregulation yes 68770 13 1 1277mer-m8 downregulation

yes 67980 6 1 567mer-1a downregulation yes 72313 10 1 3167mer-1a upregulation yes 23881 65 10 3957mer-m8 downregulation yes 231506 4 2 17177mer-m8 downregulation yes 14020 15 1 2988mer downregulation yes 252972 10 1 297mer-1a upregulation yes 11938 14 1 5968mer downregulation yes 19679 12 1 16548mer upregulation yes 243272 27 2 5306 7mer-1a downregulation yes 243362 36 2 12947mer-m8 downregulation yes 12843 9 1 1728mer downregulation yes 243725 20 1 5886 7mer-1a downregulation yes 18181 12 2 647mer-m8 upregulation yes 109624 8 1 2188 7mer-1a downregulation yes 78937 18 1 4099 8mer downregulation yes 23945 18 3 3627mer-1a upregulation yes 17342 54 3 1491 7mer-1a downregulation yes 16438 4 1 3598mer downregulation yes 192193 12 1 3604 8mer downregulation yes 71779 10 1 17817mer-m8 downregulation yes 67602 5 1 15208mer downregulation yes 73178 13 1 1468mer downregulation yes 319832 6 1 7348mer downregulation yes 208647 2 1 5477mer-m8 downregulation yes 243547 7 1 15787mer-1a upregulation yes 108655 87 3 47087mer-1a upregulation yes 330401 25 1 1527mer-1a upregulation yes 14789 1 1 5518mer upregulation yes 13860 14 1 1294 7mer-1a downregulation yes 170742 3 1 4288mer upregulation yes 12606 14 1 9467mer-m8 upregulation yes 12036 12 3 868mer upregulation yes 15204 3 1 3068mer downregulation yes 233406 2 1 6877mer-m8 upregulation yes 50490 8 2 397mer-m8 downregulation yes 11535 6 1 2897mer-m8 upregulation yes 21676 117 6 79467mer-m8 downregulation yes 19647 10 1 3127mer-1a upregulation yes 57752 18 3 338mer upregulation yes 101476 5 1 1181 8mer downregulation yes 232807 5 1 4318mer upregulation yes 67224 2 1 5917mer-m8 upregulation yes 56632 21 3 4167mer-1a upregulation yes 12877 12 1 3757mer-1a upregulation yes 13690 48 4 3897mer-1a downregulation yes 50781 6 1 308mer downregulation yes 319622 12 1 5367mer-m8 downregulation yes 12577 8 2 1587mer-m8 upregulation yes 68904 34 2 3598 7mer-1a downregulation yes 78560 13 1 1255 7mer-1a downregulation yes 234267 10 1 5647mer-m8 downregulation yes 16598 2 1 2148mer upregulation yes 622675 22 1 3341 8mer upregulation yes 73945 16 1 2855 8mer downregulation yes 19724 6 1 4637mer-m8 upregulation yes 382030 5 1 1258mer downregulation yes 214627 48 3 307mer-m8 downregulation yes 19651 5 1 6727mer-m8 downregulation yes 68051 9 2 14227mer-1a upregulation yes 54446 104 2 67377mer-m8 downregulation yes 11906 27 1 29207mer-m8 upregulation yes 244650 23 2 35897mer-m8 downregulation yes 234734 2 1 3588mer upregulation yes 54384 1 1 597mer-m8 upregulation yes 102141 3 1 3727mer-m8 downregulation yes 69260 7 1 887mer-1a downregulation yes 382014 7 1 3437mer-1a upregulation yes 52335 26 1 3758 7mer-1a downregulation yes 12398 63 3 18048mer upregulation yes 72826 13 1 2827mer-1a downregulation yes 75747 1 1 2177mer-m8 downregulation yes 67398 8 1 8738mer downregulation

yes 20320 11 1 9727mer-m8 downregulation yes 11487 20 2 5097mer-1a downregulation yes 17918 12 1 1409 8mer downregulation yes 76477 1 1 3378mer downregulation yes 211586 96 6 8607mer-m8 downregulation

yes 80517 4 1 637mer-m8 downregulation yes 20660 2 1 897mer-1a downregulation yes 244895 22 1 12627mer-m8 downregulation yes 93683 19 1 2536 7mer-1a downregulation

yes 235442 18 1 3103 8mer downregulation

yes 108837 2 1 9998mer downregulation

yes 192287 6 1 12967mer-m8 downregulation yes 74769 3 1 10808mer downregulation

yes 270201 12 1 18127mer-m8 upregulation yes 69035 9 1 13087mer-1a downregulation yes 13205 41 1 1438 8mer downregulation yes 18555 8 2 5647mer-1a upregulation yes 74365 16 1 767mer-1a downregulation

yes 14265 21 1 1739 8mer downregulation yes 12111 2 1 11308mer downregulation

yes 11977 34 2 3150 8mer downregulation

yes 67117 4 1 1108mer downregulation yes 12361 36 1 10287mer-m8 downregulation yes 72018 2 1 4447mer-1a downregulation yes 14396 3 1 19277mer-m8 downregulation

yes 22589 11 1 5748mer downregulation

yes 26900 18 1 1260 8mer downregulation

Human ID x 1 AAK1 2 AATK 3 ABCG4 4 ABHD13 5 ABI3BP 6 ABL2 7 ACAN 8 ACOX1 9 ACTC1 10 ADAM10 11 ADAM15 12 ADAM19 13 ADAM23 14 ADAMTS9 15 ADAMTSL1 16 ADAMTSL3 17 ADCY3 18 ADM 19 ADO 20 ADRB1 21 AFAP1 22 AFF1 23 AFF3 24 AFF4 25 AGAP1 26 AGFG2 27 AGGF1 28 AHCYL1 29 AIFM2 30 ALPK3 31 ANGPTL2 32 ANK3 33 ANKIB1 34 ANKRD13C 35 ANKRD44 36 ANO4 37 ANO8 38 ANP32E 39 AP1AR 40 APPL1 41 AQP2 42 ARF1 43 ARFGEF2 44 ARHGAP29 45 ARHGEF10 46 ARHGEF17 47 ARID1B 48 ARID5B 49 ARMC1 50 ARPP19 51 ARRDC3 52 ARRDC4 53 ASB7 54 ASPH 55 ASTN1 56 ATG14 57 ATOX1 58 ATP11A 59 ATP2A2 60 ATP2B4 61 ATP6V1B2 62 ATP7A 63 ATP8B1 64 ATRX 65 ATXN1 66 ATXN10 67 ATXN1L 68 ATXN3 69 ATXN7 70 AURKA 71 AXL 72 AZIN1 73 B3GALT2 74 BACH1 75 BAHCC1 76 ADGRB3 77 BAZ2A 78 BAZ2B 79 BCAT2 80 BCL11A 81 BCL11B 82 BCL2L11 83 BMP7 84 BMPR2 85 BSDC1 86 BSN 87 BTG2 88 CCDC186 89 C11orf24 90 KIAA1549L 91 C11orf87 92 C16orf52 93 GID4 94 LDLRAD4 95 C18orf25 96 OSER1 97 NOL4L 98 C20orf194 99 C21orf91 100 C2CD4C 101 C2orf69 102 C5orf24 103 C5orf30 104 C5orf63 105 C6orf62 106 C8orf44-SGK3 107 LURAP1L 108 CACNA1C 109 CACNA1H 110 CACNA1I 111 CADM2 112 CALM3 113 CALN1 114 CAMK2A 115 CAMKK2 116 CASD1 117 CASK 118 CASKIN1 119 CBFA2T3 120 CBLN4 121 CCDC113 122 CCDC6 123 CCNC 124 CCNE2 125 CCNJL 126 CCT6A 127 CD2AP 128 CD69 129 CDC27 130 CDC42 131 CDC42BPA 132 CDC42EP2 133 CDCA7L 134 CDK16 135 CDK5R1 136 CDK6 137 CDKN1C 138 CEBPA 139 CELF2 140 CEND1 141 CEP350 142 CFL2 143 CHCHD10 144 CHD9 145 CHGA 146 CHMP7 147 CHRM2 148 CHRM5 149 CHST1 150 CHST7 151 CIC 152 CLDN11 153 CLEC16A 154 CLIP4 155 CNIH1 156 CNNM4 157 CNOT2 158 CNR1 159 COG3 160 COL19A1 161 COL1A2 162 COL5A1 163 COPS2 164 CPEB1 165 CPEB2 166 CPEB3 167 CPEB4 168 CPLX1 169 CPLX2 170 CPNE8 171 CREB1 172 CREB3L2 173 CRTAM 174 CSMD1 175 CSMD3 176 CSRNP3 177 CTNNBIP1 178 CTTNBP2 179 CUL3 180 CUX1 181 CXADR 182 CXXC5 183 NSG1 184 DAB2IP 185 DACT1 186 DAG1 187 DBT 188 DCAF10 189 DCAF6 190 DCAF8 191 DCC 192 DCLK2 193 DCP1A 194 DCP2 195 DCX 196 DDHD2 197 DDIT4 198 DDX3X 199 DDX3Y 200 DENND1B 201 DENND4B 202 DENND4C 203 DIRAS1 204 DKK3 205 DLG5 206 DLGAP2 207 DMP1 208 DMXL1 209 DNAJB12 210 DNAJB9 211 DNAJC27 212 DNAJC30 213 DOCK5 214 DOCK9 215 DOK5 216 DPP10 217 DPYD 218 DSC2 219 DSCAML1 220 DSTYK 221 DTX2 222 DUS2 223 DUSP1 224 DUSP10 225 DUSP5 226 DYNLT3 227 DYRK2 228 E2F3 229 EDEM1 230 EDNRB 231 EFR3A 232 EFR3B 233 EGR2 234 AGO3 235 EIF4G2 236 ELFN2 237 ELK4 238 ELOVL4 239 ELOVL6 240 EN2 241 EOMES 242 EPB41L4A 243 EPC2 244 EPG5 245 EPHA8 246 EPS8 247 ERBB2IP 248 ERC2 249 ERGIC2 250 ESRP1 251 EVI5 252 EXOC5 253 FAM110B 254 FAM110C 255 FAM117B 256 FAM126B 257 FAM133B 258 FAM135A 259 FAM150B 260 FAM160A2 261 FAM160B1 262 ZC2HC1A 263 CCSER2 264 FAM196A 265 FAM19A1 266 FAM20C 267 TMEM255A 268 FAM76B 269 FAM81A 270 FAM84A 271 FAR1 272 FARP1 273 FBN1 274 FBN2 275 FBXL17 276 FBXO28 277 FBXO32 278 FBXO33 279 FBXW7 280 FCHO2 281 FGB 282 FHL3 283 FKBP1A 284 PRR36 285 CCDC71L 286 FMN2 287 FMR1 288 FNBP4 289 FNDC3B 290 FNIP1 291 FNIP2 292 FOSL2 293 FOXG1 294 FOXN2 295 FOXN3 296 FOXP2 297 FOXP4 298 FRS2 299 FRY 300 FRYL 301 FSTL1 302 FXR1 303 FZD10 304 G3BP2 305 GALNT7 306 GAN 307 GAP43 308 GATA2 309 GATA6 310 GATAD2B 311 PAXBP1 312 GCLM 313 GDF11 314 GFPT2 315 GIGYF2 316 GIPC1 317 GIT2 318 GLCE 319 GLRA1 320 GLYR1 321 GNPDA2 322 GNS 323 GOLGA1 324 GOLGA3 325 GOLGA4 326 GPATCH8 327 GPC6 328 GPM6A 329 ADGRA2 330 GPR137C 331 GPR158 332 GPR173 333 GPR180 334 GPR85 335 GPRC5A 336 GRAMD1B 337 GRAMD3 338 GRAMD4 339 GRHL1 340 GRIA1 341 GRIA3 342 GRIA4 343 GRIP2 344 GRM2 345 GXYLT1 346 H3F3B 347 HAND1 348 HAND2 349 HAPLN1 350 HAS2 351 HAS3 352 HCN2 353 HDLBP 354 HECW1 355 HEG1 356 HERC2 357 HERC3 358 HERC4 359 HERPUD2 360 HIPK1 361 HIPK3 362 HIVEP1 363 HMGA2 364 HNF1B 365 HNRNPU 366 HOXB8 367 HOXC4 368 HOXC8 369 HOXD10 370 HSPE1-MOB4 371 IBTK 372 ICK 373 IDH1 374 IKZF1 375 IKZF2 376 IKZF4 377 IL6ST 378 IMPA2 379 ING2 380 INSIG1 381 INSL5 382 IQGAP2 383 IRS2 384 ITGA5 385 ITGA6 386 ITGAV 387 ITM2B 388 ITPR1 389 ITPRIPL2 390 JAKMIP1 391 JARID2 392 JMY 393 JOSD1 394 JPH2 395 KALRN 396 KAT2B 397 KBTBD8 398 KCNA1 399 KCNC4 400 KCND2 401 KCNH1 402 KCNJ3 403 KCNK10 404 KCNK3 405 KCNN3 406 GLTSCR1L 407 KIAA1024 408 KIAA1109 409 KIAA1211 410 KIF1BP 411 MAP10 412 RIC1 413 KIF1B 414 KIF3B 415 KIF5B 416 KLF12 417 KLF2 418 KLF3 419 KLF4 420 KLF6 421 KLHDC10 422 KLHL14 423 KLHL15 424 KLHL18 425 KLHL29 426 KLHL3 427 KLHL31 428 KSR2 429 LAMP2 430 LATS2 431 LBX1 432 LCOR 433 P3H3 434 LHFPL2 435 LIMCH1 436 LIN28A 437 LIN54 438 LMBR1L 439 LMO2 440 TPBGL 441 LONRF3 442 LPP 443 LRCH1 444 LRRC20 445 LRRC4 446 PPP1R37 447 LRRC8B 448 LRRFIP2 449 LUZP1 450 LYST 451 MAFK 452 MAN2A1 453 MAP1B 454 MAP2K4 455 MAP3K13 456 MAP3K2 457 MAP4K2 458 4-Mar 459 MARK1 460 MAST4 461 MBD2 462 MBNL3 463 MBOAT2 464 MCL1 465 MCOLN2 466 MDGA1 467 MED29 468 MEF2D 469 MFHAS1 470 MGLL 471 MIA3 472 MIER3 473 MITF 474 MKL2 475 MMD 476 MMP16 477 MOB4 478 MORC3 479 MPP1 480 MRPS25 481 MS4A2 482 MSRB3 483 MTDH 484 MTF1 485 MTF2 486 MTHFD2 487 MTMR9 488 MYCBP2 489 MYH9 490 MYLIP 491 MYO1B 492 MYO5A 493 MYT1L 494 N4BP2 495 NAA15 496 NAA50 497 NACC2 498 NAV3 499 NCKAP5 500 NCOA1 501 NCOA3 502 NECAP1 503 NEDD4L 504 NEFH 505 NEFL 506 NEFM 507 NEGR1 508 NSMF 509 NEO1 510 NETO1 511 NEURL1B 512 NF1 513 NF2 514 NFAT5 515 NFATC2IP 516 NFIA 517 NFIB 518 NFIX 519 NFYB 520 NFYC 521 NINL 522 NIPBL 523 NKPD1 524 NKX2-3 525 NKX2-4 526 NLK 527 NOTCH1 528 NOVA1 529 NOX4 530 NPC1 531 NPHP3 532 NPNT 533 NPTN 534 NR4A3 535 NRF1 536 NRK 537 NSF 538 NSMAF 539 NUCKS1 540 NUDCD3 541 NUFIP2 542 NUP43 543 OAZ3 544 OTUD3 545 OTUD4 546 OXSR1 547 PAIP1 548 PALLD 549 PALM2 550 PANK3 551 PAPD5 552 PAPD7 553 PAQR7 554 PARP8 555 PAX3 556 PAX9 557 PCDH10 558 PCDH11X 559 PCDH11Y 560 PCDH7 561 PCDH9 562 PCGF3 563 PCMTD1 564 PCOLCE2 565 PCYT1B 566 PDCD6IP 567 PDE10A 568 PDE4D 569 PDE8A 570 PDS5A 571 PDS5B 572 PDXDC1 573 PDZD2 574 PEAK1 575 PER2 576 PEX3 577 PFKFB4 578 PGAM1 579 JADE2 580 JADE1 581 PHF3 582 PHLPP2 583 PHTF2 584 PIK3AP1 585 PIK3R3 586 PIKFYVE 587 PIP4K2C 588 PIP5K1C 589 PITPNA 590 PITPNC1 591 PITPNM2 592 PKDCC 593 PLEKHA1 594 PLEKHA6 595 PLEKHB2 596 PLEKHG3 597 PLEKHM1 598 PMEPA1 599 POLK 600 PPAP2B 601 PPARGC1B 602 PPCS 603 PPM1H 604 PPP1R12A 605 PPP1R12C 606 PPP1R3D 607 PPP1R9A 608 DESI1 609 PRDM13 610 PRDM15 611 PRDM16 612 PRKAB2 613 PRKAR1B 614 PRKAR2B 615 PRKCE 616 PRPF40A 617 PRRC2B 618 PSMD14 619 PTAR1 620 PTEN 621 PTF1A 622 PTGER4 623 PTPN14 624 PTPRD 625 PTPRJ 626 PTPRK 627 PTPRO 628 PVRL1 629 QKI 630 QSER1 631 RAB14 632 RAB23 633 RAB3B 634 RAB8B 635 RAD21 636 RAG1 637 RANBP9 638 RAP1A 639 RAP1B 640 RASSF2 641 RASSF3 642 RBBP6 643 RBFOX1 644 RBFOX2 645 RBL2 646 RBM27 647 RBM47 648 RBPMS2 649 RECK 650 REST 651 REV3L 652 REXO1 653 RFX1 654 RFX7 655 RGL1 656 RGS17 657 RGS3 658 RHPN2 659 RIMBP2 660 RIMS2 661 RNF10 662 RNF11 663 RNF141 664 RNF157 665 RNF166 666 RNF180 667 RNF38 668 RNF4 669 RNF44 670 ROBO1 671 ROBO2 672 RORA 673 RPL15 674 RPS6KA4 675 RRBP1 676 RRN3 677 RSBN1 678 RUNX1T1 679 RYR3 680 S1PR1 681 SAR1B 682 SATB2 683 SBK1 684 SBNO1 685 SCAF11 686 SCRG1 687 SCUBE3 688 SDC2 689 SDC3 690 SEC24C 691 SEC31B 692 SEL1L3 693 SELT 694 SEMA3A 695 SEMA6D 696 SERINC5 697 SERTAD2 698 SERTAD3 699 SESN3 700 SESTD1 701 SETD1B 702 SETD5 703 SETD7 704 SFMBT2 705 SGK1 706 SGK3 707 SH3D19 708 SH3PXD2A 709 SHOX 710 SIK1 711 SIM2 712 SIRPA 713 SKI 714 SLC12A2 715 SLC12A5 716 SLC16A6 717 SLC17A6 718 SLC24A3 719 SLC24A4 720 SLC25A32 721 SLC25A36 722 SLC2A3 723 SLC30A7 724 SLC32A1 725 SLC37A3 726 SLC39A6 727 SLC45A3 728 SLC4A10 729 SLC6A1 730 SLC7A11 731 SLC9A1 732 SLC9A2 733 SLC9A3R2 734 SLX4 735 SMAD6 736 SMAD7 737 SMARCA5 738 SMURF1 739 SNAI1 740 SNAP91 741 SNAPC1 742 SNN 743 SNX13 744 SNX30 745 SOBP 746 SOCS6 747 SORCS3 748 SORL1 749 SOSTDC1 750 SOX11 751 SOX4 752 SP1 753 SPHK2 754 SPOCK2 755 SPRYD4 756 SPTBN4 757 SRPK2 758 SRPR 759 SRSF3 760 SSBP3 761 SSFA2 762 ST3GAL2 763 ST6GAL2 764 STAG2 765 STARD13 766 STIM2 767 STK39 768 STRN 769 STRN3 770 STX17 771 STXBP5L 772 STYX 773 SUDS3 774 SUN1 775 SUV420H1 776 SYN2 777 SYNDIG1 778 SYNJ1 779 SYT1 780 SYT2 781 TACC2 782 TAF1 783 TAF15 784 TAGAP 785 TBC1D12 786 TBC1D30 787 TBC1D8 788 TBL1XR1 789 TBX3 790 TCEB3 791 TCF21 792 TCF4 793 TEAD1 794 TECPR2 795 TEF 796 TEX2 797 TFAP2A 798 TFAP2E 799 TFDP2 800 TGFB2 801 TGIF1 802 TIA1 803 TMC7 804 TMCC1 805 TMCC3 806 TMED5 807 TMEM143 808 TMEM184B 809 CNEP1R1 810 TMEM200B 811 TMEM229A 812 TMEM50B 813 TMEM87A 814 TMF1 815 TNPO1 816 TNRC6B 817 TOB1 818 TOB2 819 TOP1 820 TOR1AIP2 821 TP63 822 TPCN1 823 TPM4 824 TPPP 825 TRAF3 826 TRAK2 827 TRAM2 828 TRIO 829 TSC1 830 CEP41 831 TTC14 832 TTC28 833 TTC9 834 TTPAL 835 TULP4 836 TWF1 837 TWIST1 838 UBASH3B 839 UBE2G1 840 UBE2W 841 UBE2Z 842 UBXN4 843 UGP2 844 UHRF1BP1 845 ULK1 846 UQCRB 847 USF2 848 USP28 849 USP44 850 USP45 851 UVRAG 852 VCL 853 VPS4B 854 VPS54 855 VWA5B2 856 WASL 857 WDFY3 858 WDR37 859 WDR81 860 WNT5A 861 WRNIP1 862 WWC1 863 WWP2 864 XPNPEP3 865 XPR1 866 XRN1 867 XYLT2 868 ZAK 869 ZBTB34 870 ZBTB40 871 ZBTB46 872 ZCCHC2 873 ZDHHC21 874 ZDHHC3 875 ZDHHC5 876 ZEB2 877 ZFC3H1 878 ZFHX3 879 ZFHX4 880 ZFPM2 881 ZFYVE21 882 ZNF148 883 ZBTB18 884 ZNF287 885 ZNF385B 886 ZNF385D 887 ZNF469 888 ZNF512B 889 ZNF521 890 ZNF532 891 ZNF652 892 ZNF654 893 ZNHIT6 Mouse ID x 1 Lgalsl 2 1810055G02Rik 3 Fam210b 4 Ccdc71l 5 Oser1 6 Pp2d1 7 4932438A13Rik 8 Gid4 9 8030462N17Rik 10 Nol4l 11 A830010M20Rik 12 Aars 13 Aatk 14 Abat 15 Abcg4 16 Abhd13 17 Abi3bp 18 Adam10 19 Adam19 20 Adam23 21 Adamtsl1 22 Adamtsl3 23 Adcy3 24 Adm 25 Ado 26 Aff4 27 Ahcyl1 28 AI593442 29 Aida 30 Akap10 31 Akt1 32 Alpk3 33 Alx4 34 Angptl2 35 Ankib1 36 Ankrd44 37 Ano8 38 Anp32e 39 Appl1 40 Aqp2 41 Arf1 42 Arhgap29 43 Arhgef17 44 Arid1b 45 Armc1 46 Armc2 47 Arpp19 48 Arrdc3 49 Arrdc4 50 Astn1 51 Asxl2 52 Atg14 53 Atp2a2 54 Atp7a 55 Atp8b1 56 Atrx 57 Atxn1 58 Atxn1l 59 Avl9 60 Azin1 61 Zak 62 B230219D22Rik 63 B3galt2 64 Bach1 65 Bahcc1 66 Adgrb3 67 Baz2a 68 Baz2b 69 BC030336 70 Gltscr1l 71 Bcat2 72 Bcl11a 73 Bcl11b 74 Bcl2l11 75 Bend7 76 Bgn 77 Bmpr1a 78 Braf 79 Bsdc1 80 Bsn 81 Btg2 82 Ric1 83 Peak1 84 C530008M17Rik 85 Cacna1c 86 Cacna1h 87 Cacna1i 88 Cadm2 89 Cald1 90 Calm3 91 Caln1 92 Cand1 93 Cask 94 Casz1 95 Cbfa2t3 96 Ccnc 97 Ccne2 98 Ccnjl 99 Ccnl2 100 Cd2ap 101 Cd69 102 Cdc42 103 Cdc42bpa 104 Cdca7l 105 Cdk16 106 Cdkn1c 107 Cebpa 108 Cend1 109 Cep350 110 Chd9 111 Chga 112 Chka 113 Chmp7 114 Chrm2 115 Cic 116 Cldn11 117 Clec16a 118 Clip4 119 Cnnm4 120 Cnot2 121 Cntn1 122 Cog3 123 Col1a2 124 Col27a1 125 Cops2 126 Coro2a 127 Cpeb1 128 Cpeb2 129 Cpeb3 130 Cplx1 131 Creb1 132 Creb3l2 133 Csmd1 134 Csmd3 135 Ctnnbip1 136 Cxxc5 137 D16Ertd472e 138 Ldlrad4 139 Daam1 140 Dab2ip 141 Dbt 142 Dcaf6 143 Dcaf8 144 Dcbld1 145 Dcc 146 Dclk2 147 Dcp1a 148 Dcx 149 Ddit4 150 Ddx3x 151 Ddx3y 152 Dennd1b 153 Dennd4b 154 Diras1 155 Dkk3 156 Dmxl1 157 Dnajb9 158 Dnajc30 159 Dnajc4 160 Dnmt3a 161 Dock5 162 Dock9 163 Dpp10 164 Dsc2 165 Dscaml1 166 Dtx2 167 Dus2 168 Dusp10 169 Dynlt3 170 E2f3 171 Edem1 172 Efr3a 173 Ago3 174 Eif4g2 175 Eif5b 176 Elk4 177 Elovl4 178 En2 179 Eomes 180 Epc2 181 Epha8 182 Eps8 183 Erc2 184 Ergic2 185 Evi5 186 Exoc5 187 Fam110b 188 Fam126b 189 Fam135a 190 Fam160b1 191 Fam196a 192 Fam196b 193 Fam19a1 194 Fam20c 195 Fam76b 196 Fam84a 197 Farp1 198 Fbn1 199 Fbn2 200 Fbxo28 201 Fbxo33 202 Fbxw7 203 Fcho2 204 Fhl3 205 Fkbp1a 206 Fmn2 207 Fmr1 208 Fnbp4 209 Fndc3b 210 Fnip1 211 Fnip2 212 Fosl2 213 Foxg1 214 Foxn2 215 Foxp1 216 Foxp2 217 Frs2 218 Fry 219 Fryl 220 Fst 221 Fstl1 222 Fubp1 223 Fundc1 224 Fzd10 225 G3bp2 226 Gabra3 227 Gap43 228 Gata2 229 Gata6 230 Gca 231 Paxbp1 232 Gdf11 233 Gfpt2 234 Git2 235 Glce 236 Glyr1 237 Gm4980 238 Gnaq 239 Gnpda2 240 Golga1 241 Golga4 242 Gpatch8 243 Gpc6 244 Gpm6a 245 Adgra3 246 Gpr158 247 Gpr173 248 Gpr180 249 Gpr85 250 Gramd1b 251 Gramd3 252 Greb1l 253 Grhl1 254 Grhl2 255 Gria1 256 Gria3 257 Grip2 258 Grm2 259 Grm7 260 Gtf2a1 261 Gucy1a3 262 Gxylt1 263 H3f3b 264 Hand1 265 Hand2 266 Has2 267 Has3 268 Hcn2 269 Hecw1 270 Herc2 271 Herpud2 272 Hhip 273 Hif1a 274 Hipk3 275 Hivep1 276 Hmga2 277 Hmx3 278 Hnf1b 279 Hnrnpu 280 Hoxa3 281 Hoxc4 282 Hoxc8 283 Hoxd10 284 Hps6 285 Ibsp 286 Ibtk 287 Ikzf1 288 Ikzf2 289 Ing2 290 Ing5 291 Insig1 292 Iqgap2 293 Isca1 294 Itga5 295 Itga6 296 Itga8 297 Itgav 298 Itpr1 299 Itpripl2 300 Jarid2 301 Jmy 302 Josd1 303 Kalrn 304 Kat2b 305 Kcna1 306 Kcnc4 307 Kcnd2 308 Kcnk3 309 Kctd8 310 Kif3b 311 Kif5b 312 Klf12 313 Klf2 314 Klf4 315 Klhdc10 316 Klhl14 317 Klhl18 318 Klhl29 319 Lats1 320 Lats2 321 P3h3 322 Lhfpl2 323 Limch1 324 Lin28a 325 Lin54 326 Lmbr1l 327 Lmo2 328 Lonrf3 329 Lpin1 330 Lpp 331 Lrrc4 332 Ppp1r37 333 Lrrc8d 334 Luzp1 335 Mafk 336 Man2a1 337 Map2k4 338 Mapk8 339 8-Mar 340 Mark1 341 Mast4 342 Mboat2 343 Slc25a51 344 Mcl1 345 Med13 346 Med19 347 Med29 348 Megf10 349 Mfhas1 350 Mgll 351 Mia3 352 Micall1 353 Mier3 354 Mitf 355 Mmd 356 Mmp16 357 Morc3 358 Mpp1 359 Map1b 360 Mtdh 361 Mtf1 362 Mtf2 363 Mtmr7 364 Mycbp2 365 Myh9 366 Mylip 367 Myo10 368 Myo18a 369 Myo1b 370 Myo5a 371 Myt1l 372 Naa15 373 Nacc2 374 Nckap5 375 Ncoa3 376 Necap1 377 Nefm 378 Negr1 379 Nsmf 380 Neurl1b 381 Nfat5 382 Nfatc2ip 383 Nfia 384 Nfib 385 Nhlh2 386 Nkx2-3 387 Nlk 388 Nol7 389 Notch1 390 Nova1 391 Nox4 392 Npc1 393 Npnt 394 Nptn 395 Nrf1 396 Nsf 397 Nsg1 398 Nsmaf 399 Nucks1 400 Nudcd3 401 Nufip2 402 Nutf2 403 Oaz3 404 Osbpl8 405 Otud4 406 Paip1 407 Pank3 408 Papd5 409 Papd7 410 Pard3 411 Pax3 412 Pax9 413 Pcdh10 414 Pcdh7 415 Pcdh9 416 Pcgf3 417 Pcmtd1 418 Pcolce2 419 Pcyt1b 420 Pde10a 421 Pde4d 422 Pds5b 423 Pdzd2 424 Pdzd8 425 Per2 426 Pex3 427 Pgam1 428 Jade2 429 Jade1 430 Phf3 431 Phldb2 432 Phlpp2 433 Phtf2 434 Pik3ca 435 Pik3cb 436 Pik3r3 437 Pikfyve 438 Pip4k2c 439 Pip5k1c 440 Pitpna 441 Pitpnc1 442 Pitpnm2 443 Pkdcc 444 Plcxd2 445 Plekha1 446 Plekha6 447 Plekhm1 448 Pmepa1 449 Polk 450 Ppcs 451 Ppip5k2 452 Ppm1h 453 Ppp1r12c 454 Ppp1r9a 455 Desi1 456 Prc1 457 Prdm13 458 Prdm16 459 Prkaa2 460 Prkab2 461 Prkar1a 462 Prkar2b 463 Prkce 464 Prrc2b 465 Ptar1 466 Pten 467 Ptger4 468 Ptpn14 469 Ptprd 470 Ptprg 471 Ptprj 472 Ptprk 473 Ptpro 474 Pvrl1 475 Qk 476 Qser1 477 Rab11fip2 478 Rab14 479 Rab23 480 Rab3c 481 Rab8b 482 Rabgap1l 483 Rad21 484 Ranbp9 485 Rap1a 486 Rap1b 487 Rassf2 488 Rassf3 489 Rbbp6 490 Rbfox2 491 Rbl2 492 Rbm27 493 Rbm47 494 Rbpj 495 Rbpms2 496 Rev3l 497 Rfx1 498 Rfx7 499 Rgs17 500 Rgs3 501 Rhpn2 502 Rnf157 503 Rnf38 504 Rnf4 505 Rnf44 506 Robo1 507 Robo2 508 Rpl15 509 Rps6ka4 510 Rrbp1 511 Rsbn1 512 Runx1t1 513 S1pr1 514 Sar1b 515 Sbk1 516 Sbno1 517 Scn3a 518 Scn8a 519 Sdc2 520 Sdc3 521 Sec24c 522 Sema3a 523 Serpinf1 524 Sertad2 525 Sertad3 526 Sesn3 527 Setd5 528 Sfmbt2 529 Pnisr 530 Sfxn1 531 Sgk1 532 Sgk3 533 Sgms2 534 Sh3pxd2a 535 Sik1 536 Sim2 537 Ski 538 Skor1 539 Slc12a2 540 Slc12a5 541 Slc17a6 542 Slc1a1 543 Slc24a3 544 Slc25a31 545 Slc25a32 546 Slc25a36 547 Slc32a1 548 Slc41a1 549 Slc45a3 550 Slc45a4 551 Slc6a1 552 Slc9a1 553 Slc9a3r2 554 Slx4 555 Smad6 556 Smad7 557 Smurf1 558 Snap91 559 Snapc1 560 Snn 561 Snx13 562 Snx25 563 Snx30 564 Sobp 565 Sorl1 566 Sox11 567 Sp1 568 Sphk2 569 Spryd4 570 Srpk2 571 Srpr 572 Ssbp2 573 Ssbp3 574 Ssfa2 575 Stard13 576 Stk39 577 Strn 578 Strn3 579 Stx17 580 Styx 581 Sun1 582 Suv420h1 583 Syn2 584 Syne1 585 Synj1 586 Tacc2 587 Tagap 588 Tagap1 589 Tbc1d12 590 Tbc1d19 591 Tbl1xr1 592 Tbx20 593 Tbx3 594 Tceb3 595 Tcf21 596 Tcf4 597 Tead1 598 Tecpr2 599 Tef 600 Tet2 601 Tfdp2 602 Tgif1 603 Tmcc1 604 Tmem184b 605 Cnep1r1 606 Tmem229a 607 Tmem87a 608 Syndig1 609 Tnrc6b 610 Tob1 611 Tob2 612 Top1 613 Tor1aip2 614 Tpcn1 615 Traf3 616 Trak2 617 Trim36 618 Trio 619 Trip12 620 Trove2 621 Tsc1 622 Cep41 623 Ttc14 624 Ttc28 625 Ttc9 626 Ttpal 627 Tub 628 Tulp4 629 Twist1 630 Ubash3b 631 Ube2g1 632 Ube2w 633 Ube2z 634 Ugp2 635 Uhrf1bp1 636 Usf2 637 Usp28 638 Usp36 639 Vps54 640 Vwa5b2 641 Wasl 642 Wwp2 643 Xylt2 644 Yipf4 645 Zbtb34 646 Zbtb40 647 Zcchc2 648 Zdhhc21 649 Zdhhc3 650 Zdhhc5 651 Zeb2 652 Zfc3h1 653 Zfhx3 654 Zfhx4 655 Zfp148 656 Zbtb18 657 Zfp287 658 Zfp385b 659 Zfp521 660 Zfp597 661 Zfp654 662 Zfp711 663 Zfp804a 664 Zfp827 665 Zfpm2 666 Zfyve21 667 Znf512b targetsite targetseedregulation targetsite 464 464 8mer downregulation 1637 16378mer downregulation 8mer upregulation 469 7mer-m8upregulation 1818 7mer-1a upregulation 1206 309 8mer downregulation 466 7mer-m8 downregulation 2692 7mer-m8 downregulation 8mer upregulation 1797 57 7mer-1a downregulation 7mer-m8upregulation 297 246 7mer-m8 downregulation 4588 7mer-1a downregulation 1122 7mer-1a downregulation 1645 8mer downregulation 7mer-m8upregulation 2159 4368 43688mer downregulation 235 7mer-1a downregulation 2325 7mer-m8 downregulation 7mer-m8upregulation 2803 857 7mer-1a downregulation 8mer upregulation 1406 2069 20697mer-1a downregulation 3415 7mer-1a downregulation 8mer upregulation 754 6614 66147mer-1a downregulation 305 305 8mer downregulation 181 8mer downregulation 460 7mer-1a downregulation 7mer-1a upregulation 230 45 457mer-m8 downregulation 2572 8mer downregulation 256 2567mer-m8 downregulation 851 7mer-m8 downregulation 6090 8mer downregulation 1355 8mer downregulation 1098 10987mer-1a downregulation 1797 8mer upregulation 1797 520 520 7mer-1a downregulation 441 7mer-m8 downregulation 977 7mer-m8 downregulation 2159 7mer-m8 downregulation 7mer-m8upregulation 2159 7mer-m8upregulation 2159 8mer upregulation 1340 6177 61777mer-1a downregulation 2948 29487mer-1a downregulation 4821 48217mer-m8 downregulation 282 8mer downregulation 7mer-1a upregulation 1033 192 7mer-1a downregulation 117 7mer-1a downregulation 407 8mer downregulation 8mer upregulation 2224 2224 33007mer-1a downregulation 7mer-1a upregulation 1045 1045 5997mer-m8 downregulation 7mer-m8upregulation 474 239 7mer-m8 downregulation 8mer upregulation 321 1841 8mer downregulation 963 963 8mer downregulation 680 7mer-m8 downregulation 4315 43157mer-m8 downregulation 7mer-m8upregulation 1189 728 7mer-1a downregulation 254 254 8mer downregulation 7mer-m8upregulation 344 1134 7mer-m8 downregulation 826 7mer-1aupregulation 826 2854 7mer-1a downregulation 7mer-1a upregulation 2207 777 7mer-1a downregulation 2978 29787mer-m8 downregulation 1199 11997mer-m8 downregulation 654 6547mer-m8 downregulation 1234 7mer-1a downregulation 1390 8mer downregulation 7mer-1a upregulation 1829 8mer upregulation 114 137 8mer downregulation 3308 7mer-1a downregulation 3020 7mer-m8 downregulation 354 7mer-m8 downregulation 323 8mer downregulation 2710 7mer-1a downregulation 229 229 7mer-1a downregulation 1090 8mer downregulation 206 206 8mer downregulation 250 250 8mer downregulation 7mer-1a upregulation 457 5353 53537mer-1a downregulation 2399 23998mer downregulation 249 7mer-1a downregulation 2534 8mer downregulation 138 138 7mer-1a downregulation 1377 8mer downregulation 7mer-m8upregulation 6618 7mer-m8upregulation 701 510 5107mer-m8 downregulation 365 365 8mer downregulation 656 8mer downregulation 1804 18047mer-m8 downregulation 8mer upregulation 1878 2238 7mer-1a downregulation 2246 7mer-m8 downregulation 230 8mer downregulation 3104 7mer-1a downregulation 174 7mer-m8 downregulation 7mer-1a upregulation 223 1171 7mer-1a downregulation 92 8mer downregulation 503 8mer downregulation 82 82 7mer-1a downregulation 1377 8mer downregulation 1504 8mer downregulation 510 7mer-m8 downregulation 1301 7mer-m8 downregulation 283 8mer downregulation 1726 8mer downregulation 871 7mer-1a downregulation 8mer upregulation 1265 1430 7mer-1a downregulation 1153 7mer-m8 downregulation 325 325 7mer-1a downregulation 2269 7mer-1a downregulation 8mer upregulation 1884 7mer-m8upregulation 1037 4124 41247mer-1a downregulation 1062 10628mer downregulation 512 8mer downregulation 612 8mer downregulation 511 7mer-1a downregulation 1705 7mer-m8 downregulation 1454 7mer-1a downregulation 7mer-1a upregulation 668 2695 26958mer downregulation 172 7mer-m8 downregulation 380 7mer-m8 downregulation 2416 24167mer-1a downregulation 537 537 7mer-1a downregulation 465 8mer downregulation 1169 8mer downregulation 7mer-1a upregulation 233 1377 7mer-m8 downregulation 455 7mer-m8 downregulation 8mer upregulation 136 473 7mer-m8 downregulation 8mer upregulation 1062 8mer upregulation 285 7mer-1a upregulation 1808 8mer upregulation 290 1376 8mer downregulation 576 7mer-1a downregulation 877 8mer downregulation 7mer-m8upregulation 1682 1524 8mer downregulation 1321 7mer-1a downregulation 7mer-m8upregulation 3176 8mer upregulation 234 7mer-m8upregulation 304 105 7mer-m8upregulation 105 7mer-1a upregulation 907 864 7mer-m8 downregulation 8mer upregulation 1200 8mer upregulation 1565 3762 37627mer-m8 downregulation 2436 24368mer downregulation 728 7mer-1a downregulation 2510 25108mer downregulation 7mer-1a upregulation 2912 2914 7mer-m8 downregulation 7mer-1a upregulation 267 206 7mer-1a downregulation 248 2487mer-m8 downregulation 7mer-1a upregulation 808 2856 28568mer downregulation 2265 7mer-m8 downregulation 1387 8mer downregulation 446 8mer downregulation 4903 49037mer-m8 downregulation 512 5127mer-m8 downregulation 101 8mer downregulation 592 7mer-m8 downregulation 4237 8mer downregulation 8mer upregulation 2385 5556 7mer-m8 downregulation 1083 10837mer-m8 downregulation 3935 39358mer downregulation 7mer-m8upregulation 1318 3363 7mer-1a downregulation 275 7mer-1a downregulation 2484 24848mer downregulation 38 8mer downregulation 638 8mer downregulation 128 8mer downregulation 468 468 8mer downregulation 1815 18158mer downregulation 628 628 7mer-1a downregulation 1923 7mer-1a downregulation 1915 8mer downregulation 8mer upregulation 349 772 8mer downregulation 8mer upregulation 117 8mer upregulation 867 268 8mer downregulation 1787 7mer-1a downregulation 1761 17617mer-1a downregulation 609 8mer downregulation 1176 8mer downregulation 7mer-m8upregulation 1318 7mer-m8upregulation 705 465 7mer-m8 downregulation 62 62 7mer-1a downregulation 647 7mer-1a downregulation 725 7mer-1a downregulation 2512 25127mer-m8 downregulation 7mer-1a upregulation 3750 2361 8mer downregulation 84 7mer-1a downregulation 2809 8mer upregulation 2809 1365 7mer-m8 downregulation 481 7mer-1a downregulation 1159 7mer-1a downregulation 1769 17697mer-1a downregulation 909 7mer-1a downregulation 7mer-1a upregulation 786 30 8mer downregulation 2247 22478mer downregulation 7mer-m8upregulation 909 647 7mer-1a downregulation 542 542 7mer-1a downregulation 364 8mer downregulation 1776 7mer-m8 downregulation 266 8mer downregulation 940 7mer-m8 downregulation 1376 7mer-1a downregulation 56 7mer-1a downregulation 569 7mer-m8 downregulation 319 8mer downregulation 8mer upregulation 110 2329 8mer upregulation 2329 2206 7mer-1a downregulation 3908 39088mer downregulation 8mer upregulation 316 947 8mer downregulation 2516 8mer downregulation 2667 7mer-1a downregulation 2269 8mer downregulation 7mer-1a upregulation 268 10940 109407mer-m8 downregulation 3388 33887mer-1a downregulation 135 135 7mer-1a downregulation 981 7mer-m8 downregulation 1059 10597mer-1a downregulation 97 7mer-m8 downregulation 3295 7mer-1a downregulation 7mer-1a upregulation 793 281 7mer-m8 downregulation 936 8mer upregulation 936 4050 7mer-m8 downregulation 644 8mer upregulation 644 212 7mer-m8 downregulation 362 7mer-m8 downregulation 34 7mer-1a downregulation 981 7mer-m8 downregulation 2835 7mer-1a downregulation 4219 8mer downregulation 72 727mer-m8 downregulation 1699 8mer downregulation 895 8mer downregulation 7mer-1a upregulation 793 515 8mer downregulation 1746 8mer downregulation 8mer upregulation 160 4591 8mer downregulation 446 7mer-m8 downregulation 3958 7mer-1a downregulation 1727 17278mer downregulation 7mer-m8upregulation 664 7mer-1a upregulation 1308 368 3687mer-m8 downregulation 8mer upregulation 122 1671 7mer-m8 downregulation 2607 8mer downregulation 8mer upregulation 160 2069 20697mer-1a downregulation 7mer-1a upregulation 433 7mer-1a upregulation 717 753 8mer upregulation 753 3100 31007mer-m8 downregulation 2902 7mer-1a downregulation 8mer upregulation 340 8mer upregulation 304 574 574 7mer-1a downregulation 160 8mer downregulation 1640 8mer downregulation 655 7mer-m8 downregulation 7mer-m8upregulation 38 2936 7mer-1a downregulation 1562 15628mer downregulation 185 8mer downregulation 3388 7mer-1a downregulation 2731 27317mer-1a downregulation 989 7mer-1a downregulation 434 7mer-1a downregulation 7mer-m8upregulation 1377 188 1887mer-m8 downregulation 975 7mer-1a downregulation 565 7mer-1a downregulation 509 8mer downregulation 1714 7mer-m8 downregulation 8mer upregulation 1780 1612 7mer-1a downregulation 2240 22408mer downregulation 7mer-1a upregulation 5150 637 7mer-1a downregulation 7mer-m8upregulation 79 177 7mer-m8 downregulation 233 8mer upregulation 233 1959 7mer-m8 downregulation 34 34 8mer downregulation 7mer-1a upregulation 550 1574 15748mer downregulation 2860 8mer downregulation 263 263 7mer-1a downregulation 8mer upregulation 878 833 8mer downregulation 8mer upregulation 62 2346 23468mer downregulation 7mer-m8upregulation 434 2946 8mer downregulation 4715 7mer-m8 downregulation 2162 21628mer downregulation 3546 35467mer-1a downregulation 261 7mer-m8 downregulation 232 8mer downregulation 1760 17607mer-m8 downregulation 3751 8mer downregulation 2828 7mer-1a downregulation 7mer-m8upregulation 320 7mer-1a upregulation 1587 284 8mer downregulation 2328 23288mer downregulation 1403 14037mer-1a downregulation 2713 7mer-m8 downregulation 868 7mer-1a downregulation 2271 7mer-m8 downregulation 638 638 8mer downregulation 5113 7mer-1a downregulation 398 8mer downregulation 412 7mer-1a downregulation 3080 30808mer downregulation 7mer-m8upregulation 245 7mer-m8upregulation 349 7mer-1a upregulation 3755 352 3527mer-m8 downregulation 2845 28457mer-m8 downregulation 44 44 8mer downregulation 370 8mer downregulation 7mer-1a upregulation 1073 1653 16537mer-m8 downregulation 595 7mer-m8 downregulation 381 7mer-1a downregulation 556 7mer-1a downregulation 7mer-1a upregulation 2228 7mer-1a upregulation 616 578 7mer-1a downregulation 1402 14028mer downregulation 3801 38017mer-1a downregulation 1587 7mer-1a downregulation 4562 7mer-1a downregulation 1914 19148mer downregulation 1870 8mer downregulation 865 8657mer-m8 downregulation 335 335 8mer downregulation 1929 7mer-m8 downregulation 1084 7mer-m8 downregulation 1008 7mer-1a downregulation 260 7mer-m8 downregulation 1005 10058mer downregulation 900 900 7mer-1a downregulation 469 4697mer-m8 downregulation 7mer-m8upregulation 579 809 809 8mer downregulation 380 7mer-1a downregulation 2508 7mer-m8 downregulation 7mer-m8upregulation 295 1248 8mer downregulation 112 7mer-1aupregulation 112 382 7mer-1a downregulation 8mer upregulation 211 7mer-m8upregulation 1980 8mer upregulation 2347 988 8mer downregulation 1651 8mer downregulation 661 661 7mer-1a downregulation 252 252 8mer downregulation 110 7mer-1a downregulation 2847 28477mer-1a downregulation 361 7mer-1a downregulation 1208 12087mer-1a downregulation 8mer upregulation 1630 671 8mer downregulation 8mer upregulation 9 1759 7mer-m8 downregulation 2936 7mer-1a downregulation 1548 7mer-1a downregulation 1377 13778mer downregulation 472 7mer-m8 downregulation 294 2947mer-m8 downregulation 2098 7mer-m8 downregulation 378 378 7mer-1a downregulation 79 797mer-m8 downregulation 1657 16577mer-m8 downregulation 8mer upregulation 3383 831 831 7mer-1a downregulation 7mer-1a upregulation 1216 110 7mer-m8 downregulation 224 7mer-1a downregulation 892 8mer downregulation 1927 7mer-1a downregulation 1238 7mer-m8 upregulation 1238 3565 7mer-1a downregulation 154 1547mer-m8 downregulation 8mer upregulation 2209 115 7mer-m8 downregulation 492 7mer-m8 downregulation 3505 8mer downregulation 681 7mer-1a downregulation 620 8mer downregulation 8mer upregulation 1370 4737 7mer-1a downregulation 860 8607mer-m8 downregulation 8mer upregulation 517 372 8mer upregulation 372 1848 8mer downregulation 7mer-m8upregulation 946 7mer-1a upregulation 153 3202 32027mer-1a downregulation 7mer-1a upregulation 619 8mer upregulation 1238 2440 24407mer-m8 downregulation 1154 8mer downregulation 2570 25708mer downregulation 855 8557mer-m8 downregulation 560 7mer-1a downregulation 4641 7mer-1a downregulation 579 7mer-m8upregulation 579 7mer-m8upregulation 70 703 7mer-m8 downregulation 8mer upregulation 1370 3292 7mer-m8 downregulation 2908 7mer-m8 downregulation 2027 7mer-m8 upregulation 2027 8mer upregulation 751 1275 12758mer downregulation 7mer-1a upregulation 1862 746 746 7mer-1a downregulation 5116 51167mer-m8 downregulation 8mer upregulation 402 1575 7mer-1a downregulation 1934 7mer-m8 downregulation 1335 7mer-1a downregulation 1001 7mer-m8 upregulation 1001 97 7mer-1a downregulation 7mer-m8upregulation 855 4641 7mer-1a downregulation 1592 7mer-m8 downregulation 63 7mer-1a downregulation 944 9447mer-m8 downregulation 7mer-1a upregulation 57 2284 7mer-1a downregulation 597 8mer downregulation 622 622 8mer downregulation 1028 7mer-m8 downregulation 694 694 7mer-1a downregulation 286 7mer-1a downregulation 1262 12628mer downregulation 344 344 8mer downregulation 7mer-m8upregulation 2564 89 8mer downregulation 505 8mer downregulation 1711 17117mer-1a downregulation 2610 26108mer downregulation 476 7mer-1a downregulation 861 7mer-1a downregulation 670 8mer downregulation 7mer-1a upregulation 235 8mer upregulation 403 7mer-1a upregulation 357 8mer upregulation 682 1149 7mer-m8 downregulation 7mer-1a upregulation 2106 7mer-m8upregulation 355 2233 22338mer downregulation 927 9277mer-m8 downregulation 127 7mer-m8 downregulation 1289 7mer-1a downregulation 108 7mer-m8 downregulation 8mer upregulation 1742 438 7mer-1a downregulation 56 7mer-1a downregulation 316 7mer-1aupregulation 316 395 3957mer-m8 downregulation 1717 17177mer-m8 downregulation 298 298 8mer downregulation 1264 7mer-1a downregulation 7mer-1a upregulation 2748 29 7mer-1a downregulation 596 8mer downregulation 8mer upregulation 1654 5306 7mer-1a downregulation 7mer-1a upregulation 2835 1294 7mer-m8 downregulation 172 172 8mer downregulation 5886 7mer-1a downregulation 730 7mer-m8 downregulation 742 7mer-1a downregulation 64 7mer-m8 downregulation 2390 23908mer downregulation 2188 21887mer-1a downregulation 111 7mer-m8 downregulation 4099 8mer downregulation 1288 8mer upregulation 1288 362 7mer-1a downregulation 624 8mer downregulation 1491 7mer-1a downregulation 359 8mer downregulation 3604 8mer downregulation 874 7mer-1a downregulation 7mer-m8upregulation 281 7mer-1a upregulation 1237 8mer upregulation 2208 1781 7mer-m8 downregulation 1520 8mer downregulation 325 8mer downregulation 140 7mer-1a downregulation 146 8mer downregulation 734 8mer downregulation 28 7mer-1a downregulation 2204 7mer-m8 downregulation 547 5477mer-m8 downregulation 5896 8mer downregulation 7mer-1a upregulation 1578 7mer-1a upregulation 4708 7mer-1a upregulation 152 1254 7mer-1a downregulation 8mer upregulation 551 1492 8mer downregulation 8mer upregulation 714 7mer-1a upregulation 1294 65 8mer downregulation 550 8mer downregulation 8mer upregulation 428 7mer-m8upregulation 946 1166 8mer downregulation 8mer upregulation 86 177 7mer-m8 downregulation 306 306 8mer downregulation 687 7mer-m8 downregulation 7mer-1a upregulation 1255 1680 8mer downregulation 39 397mer-m8 downregulation 7mer-m8upregulation 4095 7mer-m8upregulation 289 7946 79467mer-m8 downregulation 7mer-m8upregulation 2600 7mer-1a upregulation 312 1470 7mer-1a downregulation 33 8mer upregulation 33 1181 11818mer downregulation 7mer-m8upregulation 162 431 8mer upregulation 431 7mer-1a upregulation 1043 7mer-m8upregulation 591 416 7mer-1aupregulation 416 1142 8mer downregulation 375 7mer-1aupregulation 375 7mer-1a upregulation 1398 389 389 7mer-1a downregulation 30 30 8mer downregulation 7mer-m8upregulation 7946 536 5367mer-m8 downregulation 841 8mer downregulation 7mer-m8upregulation 1933 764 7mer-1a downregulation 7mer-m8upregulation 158 3598 35987mer-1a downregulation 1255 12557mer-1a downregulation 512 8mer downregulation 564 7mer-m8 downregulation 7mer-m8upregulation 118 214 8mer upregulation 214 3341 8mer downregulation 2855 8mer downregulation 7mer-m8upregulation 463 8mer upregulation 125 30 307mer-m8 downregulation 2378 7mer-1a downregulation 672 7mer-m8 downregulation 7mer-1a upregulation 1422 8mer upregulation 270 7mer-m8upregulation 27 6737 7mer-m8 downregulation 1587 8mer downregulation 7mer-m8upregulation 2920 3589 35897mer-m8 downregulation 8mer upregulation 358 7mer-1a upregulation 32 7mer-1a upregulation 2672 7mer-m8upregulation 59 372 7mer-m8 downregulation 88 7mer-1a downregulation 7mer-1a upregulation 343 412 7mer-m8 downregulation 3758 37587mer-1a downregulation 1804 8mer downregulation 7mer-1a upregulation 32 282 7mer-1a downregulation 217 2177mer-m8 downregulation 873 8mer downregulation 8mer upregulation 2877 526 8mer downregulation 934 8mer downregulation 972 7mer-m8 downregulation 7mer-m8upregulation 926 509 509 7mer-1a downregulation 2616 7mer-1a downregulation 7mer-1a upregulation 3339 1409 8mer downregulation 337 337 8mer downregulation 860 8607mer-m8 downregulation 7mer-m8upregulation 113 354 8mer downregulation 4528 8mer downregulation 63 7mer-m8 downregulation 8mer upregulation 34 936 936 8mer downregulation 89 89 7mer-1a downregulation 667 7mer-1a downregulation 2630 7mer-1a downregulation 1262 12627mer-m8 downregulation 2536 7mer-1a downregulation 7mer-m8upregulation 405 7mer-m8upregulation 199 3103 31038mer downregulation 1237 8mer downregulation 999 999 8mer downregulation 1384 7mer-1a downregulation 1296 12967mer-m8 downregulation 1080 10808mer downregulation 87 7mer-1a downregulation 7mer-m8upregulation 3829 7mer-m8upregulation 1812 1308 7mer-1a downregulation 1438 14388mer downregulation 7mer-1a upregulation 564 76 7mer-1a downregulation 121 1217mer-m8 downregulation 1739 17398mer downregulation 1130 8mer downregulation 7mer-1a upregulation 946 3150 31508mer downregulation 890 7mer-m8 downregulation 110 8mer downregulation 1028 10287mer-m8 downregulation 444 7mer-1a downregulation 1927 19277mer-m8 downregulation 8mer upregulation 328 574 574 8mer downregulation 5908 7mer-1a downregulation 7mer-m8upregulation 605 1260 12608mer downregulation

significant eg miRNAnumtargetnum targetsite 464 1818 yes 319263 11 1 464 1637 1206 yes 170755 48 3 1637 469 no 19335 14 2 469 yes 94220 14 1 1818 yes 226982 13 1 1206 309 no 23792 16 1 309 466 yes 12912 108 3 466 2692 no 18711 15 1 2692 1797 no 18627 7 1 1797 57 yes 66262 9 1 57 297 no 227449 37 2 297 246 yes 98396 10 1 246 4588 no 98415 60 2 4588 1122 yes 212980 5 1 1122 1645 no 13714 5 1 1645 2159 no 240753 24 2 2159 4368 yes 329260 62 6 4368 235 no 26878 5 1 235 2325 yes 240832 9 1 2325 2803 no 11899 18 2 2803 857 no 98193 7 1 857 1406 no 54418 5 1 1406 2069 yes 30928 64 2 2069 3415 no 226751 11 1 3415 754 no 63953 6 1 754 6614 yes 19250 20 1 6614 305 yes 66799 15 1 305 181 yes 68187 5 1 181 460 no 210933 15 1 460 230 yes 213109 12 1 230 45 yes 17912 12 4 45 2572 yes 329154 13 1 2572 256 yes 213056 48 2 256 851 yes 70827 8 1 851 6090 no 22779 30 1 6090 1355 no 18505 16 2 1355 1098 1797 yes 14897 19 1 1098 yes 18627 7 1 1797 520 yes 227399 5 1 520 441 no 269109 3 1 441 977 no 210356 24 3 977 2159 no 240753 24 2 2159 2159 no 240753 24 2 2159 2159 no 240753 24 2 2159 1340 yes 12227 24 2 1340 6177 yes 20822 16 1 6177 2948 yes 74081 28 1 2948 4821 yes 29809 21 1 4821 282 yes 74106 2 1 282 1033 yes 51810 16 1 1033 192 yes 67948 28 1 192 117 yes 226778 12 2 117 407 no 56533 66 2 407 2224 yes 64009 21 1 2224 3300 yes 16798 22 1 3300 1045 yes 20393 84 6 1045 599 yes 19272 4 1 599 474 no 19714 12 2 474 239 no 66686 14 1 239 321 no 15166 3 1 321 1841 yes 18717 12 2 1841 963 yes 237542 24 2 963 680 no 216345 8 1 680 4315 yes 319468 5 1 4315 1189 no 116848 26 1 1189 728 yes 56535 3 1 728 254 yes 21412 3 1 254 344 no 213402 3 1 344 1134 no 109205 17 1 1134 826 yes 74747 12 1 826 2854 yes 211488 11 1 2854 2207 no 208666 10 1 2207 777 yes 72068 66 3 777 2978 yes 327826 28 1 2978 1199 yes 215449 24 2 1199 654 yes 71902 17 1 654 1234 no 15364 28 1 1234 1390 yes 192678 14 1 1390 1829 no 117150 7 1 1829 114 no 66701 2 1 114 137 yes 14561 1 1 137 3308 no 22778 18 2 3308 3020 yes 58172 40 4 3020 354 yes 245944 5 1 354 323 no 14025 39 1 323 2710 no 574403 9 1 2710 229 yes 211347 10 1 229 1090 no 380694 7 1 1090 206 yes 11492 18 1 206 250 yes 14584 9 1 250 457 yes 66397 5 1 457 5353 yes 93736 36 1 5353 2399 yes 216742 19 2 2399 249 no 14799 18 2 249 2534 yes 66771 19 1 2534 138 yes 67128 24 1 138 1377 yes 18738 16 1 1377 6618 yes 68564 74 1 6618 701 yes 360013 3 1 701 510 no 21410 6 1 510 365 yes 67468 17 1 365 656 yes 22057 9 1 656 1804 yes 19084 7 1 1804 1878 yes 268515 15 1 1878 2238 no 209586 2 1 2238 2246 yes 216551 16 1 2246 230 yes 216558 2 1 230 3104 no 76901 23 1 3104 174 no 15110 7 1 174 223 no 11840 8 2 223 1171 yes 56697 3 1 1171 92 yes 170740 5 1 92 503 yes 26398 8 2 503 82 yes 20317 2 1 82 1377 no 18738 16 1 1377 1504 yes 18099 27 1 1504 510 no 21410 6 1 510 1301 yes 327987 44 1 1301 283 no 217119 4 1 283 1726 yes 268470 20 1 1726 871 yes 237943 13 1 871 1265 no 353047 13 2 1265 1430 no 18195 6 1 1430 1153 no 71795 11 1 1153 325 no 15081 20 1 325 2269 no 217340 6 1 2269 1884 yes 72344 4 1 1884 1037 no 11302 18 3 1037 4124 yes 75302 19 2 4124 1062 yes 13435 57 1 1062 512 no 104111 18 3 512 612 no 195733 18 2 612 511 yes 67216 18 2 511 1705 no 17933 124 4 1705 1454 yes 72123 16 1 1454 668 no 22160 4 1 668 2695 yes 217463 13 1 2695 172 no 15228 26 2 172 380 no 18511 9 1 380 2416 yes 208846 38 2 2416 537 yes 15251 5 1 537 465 yes 75627 1 1 465 1169 no 69480 6 1 1169 233 no 12652 2 1 233 1377 no 104859 7 1 1377 455 yes 22031 54 2 455 136 no 68520 3 1 136 473 yes 217946 7 1 473 1062 no 13435 57 1 1062 285 no 208439 24 1 285 1808 yes 105005 13 1 1808 290 yes 14245 15 3 290 1376 no 20666 35 1 1376 576 no 19088 7 1 576 877 yes 27362 9 1 877 1682 yes 664883 77 1 1682 1524 no 94186 36 2 1524 1321 no 70611 36 1 1321 3176 yes 83602 50 2 3176 234 yes 58208 80 2 234 304 yes 11651 6 2 304 105 yes 110521 8 1 105 907 yes 70078 5 1 907 864 no 16468 69 3 864 1200 yes 218203 11 1 1200 1565 no 14057 6 1 1565 3762 yes 78521 16 1 3762 2436 yes 105171 20 1 2436 728 no 66970 24 2 728 2510 yes 218454 14 2 2510 2912 yes 238871 34 1 2912 2914 yes 218613 29 1 2914 267 yes 218693 32 2 267 206 no 94253 14 2 206 248 yes 13557 23 1 248 808 yes 56705 14 1 808 2856 yes 20238 198 9 2856 2265 yes 105239 104 4 2265 1387 yes 69046 1 1 1387 446 yes 210106 30 2 446 4903 yes 57748 21 2 4903 512 yes 544963 2 1 512 101 yes 27015 3 1 101 592 yes 218503 6 1 592 4237 no 17755 9 1 4237 2385 no 328329 13 1 2385 5556 no 67295 14 2 5556 1083 yes 14313 7 1 1083 3935 yes 19270 28 1 3935 1318 no 238988 11 1 1318 3363 no 75901 35 2 3363 275 yes 56291 26 1 275 2484 yes 23888 32 2 2484 38 no 58245 6 1 38 638 no 223254 9 1 638 128 no 66480 4 1 128 468 yes 72993 10 1 468 1815 yes 26419 10 1 1815 628 yes 12166 11 1 628 1923 no 1.01E+08 15 1 1923 1915 no 105504 9 1 1915 349 yes 50523 11 1 349 772 no 68813 3 1 772 117 no 18040 6 1 117 867 no 105513 7 1 867 268 yes 338337 8 1 268 1787 no 211712 12 1 1787 1761 yes 16597 24 1 1761 609 yes 105689 7 1 609 1176 yes 105445 36 4 1176 1318 no 238988 11 1 1318 705 yes 17909 7 1 705 465 yes 15529 11 1 465 62 no 67154 12 1 62 647 yes 252973 15 1 647 725 no 22762 30 1 725 2512 no 76740 4 1 2512 3750 no 27008 5 1 3750 2361 no 239556 7 1 2361 84 no 213988 184 2 84 2809 yes 21685 10 2 2809 1365 no 12805 9 3 1365 481 no 11827 3 1 481 1159 no 20273 100 6 1159 1769 yes 20683 36 1 1769 909 yes 15426 17 1 909 786 yes 15423 2 1 786 30 no 19219 4 2 30 2247 yes 68070 12 1 2247 909 yes 223435 7 1 909 647 no 252973 15 1 647 542 yes 54375 26 2 542 364 no 69906 2 1 364 1776 no 239420 9 2 1776 266 yes 19357 6 1 266 940 no 15117 8 1 940 1376 yes 106068 14 2 1376 56 yes 93686 138 6 56 569 yes 17886 10 1 569 319 no 223693 6 1 319 110 no 74158 12 1 110 2329 yes 57259 10 1 2329 2206 yes 28075 10 1 2206 3908 yes 223827 29 1 3908 316 yes 74775 8 1 316 947 no 16402 12 1 947 2516 yes 268860 20 2 2516 2667 no 74374 10 2 2667 2269 yes 20621 16 1 2269 268 no 328643 5 1 268 10940 yes 210126 123 3 10940 3388 yes 22661 63 1 3388 135 yes 14314 6 1 135 981 yes 433022 17 1 981 1059 yes 320712 20 5 1059 97 no 19876 8 1 97 3295 yes 12013 17 1 3295 793 no 67367 9 1 793 281 yes 338467 3 1 281 936 yes 20465 4 1 936 4050 yes 71063 4 1 4050 644 yes 52864 3 1 644 212 yes 545156 31 1 212 362 no 14432 6 1 362 34 yes 208177 7 1 34 981 no 433022 17 1 981 2835 yes 72020 21 1 2835 4219 no 239857 46 4 4219 72 yes 268902 19 1 72 1699 no 67102 14 1 1699 895 no 104015 30 2 895 793 yes 67367 9 1 793 515 no 239985 24 2 515 1746 no 68842 24 2 1746 160 no 72536 2 1 160 4591 no 23984 14 1 4591 446 yes 240055 11 2 446 3958 yes 224648 10 1 3958 1727 yes 18519 18 2 1727 664 yes 17158 18 3 664 1308 yes 78785 10 1 1308 368 yes 67864 4 1 368 122 yes 106522 5 1 122 1671 no 18754 23 1 1671 2607 yes 14236 17 1 2607 160 yes 380608 2 1 160 2069 yes 19317 120 1 2069 433 yes 65962 10 2 433 717 no 58226 10 2 717 753 yes 17691 23 1 753 3100 yes 12488 18 1 3100 2902 yes 210982 19 1 2902 340 no 110332 1 1 340 304 yes 21815 35 5 304 574 yes 268980 7 1 574 160 no 72536 2 1 160 1640 no 381157 27 1 1640 655 no 14465 8 1 655 38 no 67393 4 1 38 2936 yes 225432 9 1 2936 1562 yes 240283 13 1 1562 185 yes 107022 6 1 185 3388 no 70417 4 1 3388 2731 yes 20496 13 1 2731 989 no 52662 8 1 989 434 no 21413 86 2 434 1377 yes 17131 14 1 1377 188 yes 16573 6 1 188 975 yes 18145 5 1 975 565 no 225207 12 1 565 509 no 13506 2 1 509 1714 yes 225266 5 2 1714 1780 no 28105 20 2 1780 1612 no 14119 13 1 1612 2240 yes 54670 9 1 2240 5150 no 13176 22 1 5150 637 yes 212163 12 1 637 79 yes 72056 2 1 79 177 yes 225888 88 4 177 233 yes 12660 6 1 233 1959 yes 14682 13 2 1959 34 yes 72351 2 1 34 550 no 20510 13 1 550 1574 yes 226089 12 2 1574 2860 yes 19211 57 1 2860 263 yes 209478 10 1 263 878 no 18648 3 1 878 833 no 18089 3 1 833 62 yes 20170 1 1 62 2346 yes 226252 10 1 2346 434 yes 56613 7 1 434 2946 no 208922 41 5 2946 4715 yes 14218 62 4 4715 2162 yes 107368 8 1 2162 3546 yes 74998 31 2 3546 261 no 108909 4 1 261 232 no 338366 6 1 232 1760 yes 209645 6 2 1760 3751 no 353282 16 2 3751 2828 no 241263 11 1 2828 320 yes 56876 15 5 320 1587 no 18128 8 1 1587 284 no 64930 20 1 284 2328 yes 227723 20 2 2328 1403 yes 26360 9 1 1403 2713 no 69601 24 3 2713 868 yes 227867 28 1 868 2271 yes 227960 3 1 2271 638 yes 16403 5 1 638 5113 no 65964 11 1 5113 398 yes 70599 3 1 398 412 no 241514 3 1 412 3080 yes 16410 3 1 3080 245 no 381379 2 1 245 349 yes 55935 9 1 349 3755 no 11695 8 1 3755 352 yes 16909 8 4 352 2845 yes 12125 90 6 2845 44 no 94249 7 1 44 370 no 433485 6 1 370 1073 no 14225 9 1 1073 1653 yes 16569 10 1 1653 595 no 22348 4 1 595 381 no 21969 14 1 381 556 no 76080 12 2 556 2228 no 57138 16 3 2228 616 no 17979 12 1 616 578 yes 67017 7 1 578 1402 yes 241226 11 1 1402 3801 no 67991 48 2 3801 1587 no 18128 8 1 1587 4562 yes 241311 42 1 4562 1914 yes 68365 10 1 1914 1870 yes 76899 11 1 1870 865 yes 24136 39 1 865 335 no 407823 21 1 335 1929 no 20269 17 1 1929 1084 yes 53416 14 1 1084 1008 yes 241494 18 3 1008 260 yes 228136 13 1 260 1005 yes 19271 18 1 1005 900 yes 15259 90 8 900 469 yes 99003 19 1 469 579 no 211499 15 3 579 809 yes 14118 11 1 809 380 yes 12848 19 1 380 2508 no 215653 10 1 2508 295 yes 81910 4 1 295 1248 no 329540 66 2 1248 112 yes 66680 5 1 112 382 yes 65112 16 1 382 211 yes 269401 11 1 211 1980 no 80892 50 1 1980 2347 yes 81004 23 1 2347 988 no 18417 4 1 988 1651 no 18706 22 1 1651 661 yes 67120 7 1 661 252 yes 229227 2 1 252 110 no 73333 2 1 110 2847 yes 269424 88 4 2847 361 no 18526 33 1 361 1208 no 74838 29 1 1208 1630 yes 50754 87 6 1630 671 no 229541 4 1 671 9 no 17210 8 1 9 1759 yes 66471 5 1 1759 2936 no 108097 4 1 2936 1548 no 18072 17 1 1548 1377 no 229675 19 1 1377 472 yes 13171 4 1 472 294 yes 214137 6 1 294 2098 yes 51886 23 1 2098 378 yes 320840 18 1 378 79 yes 74252 10 2 79 1657 yes 72007 29 2 1657 3383 no 329679 19 1 3383 831 yes 60596 4 1 831 1216 no 70762 10 5 1216 110 no 53814 1 1 110 224 yes 109905 12 1 224 892 no 99738 9 1 892 1927 yes 229709 6 1 1927 1238 no 13609 13 1 1238 3565 yes 74442 26 1 3565 154 yes 114249 4 2 154 2209 yes 214133 25 1 2209 115 no 242297 2 1 115 492 no 12448 14 2 492 3505 no 12395 150 3 3505 681 no 17389 20 1 681 620 yes 51813 2 1 620 1370 yes 66625 9 1 1370 4737 yes 67727 10 1 4737 860 yes 209131 30 1 860 517 no 50780 6 1 517 372 yes 373864 9 1 372 1848 yes 77739 8 1 1848 946 yes 18027 210 6 946 153 yes 72475 18 2 153 3202 yes 18710 16 2 3202 619 yes 14201 2 1 619 1238 no 100383 8 1 1238 2440 yes 20970 6 1 2440 1154 no 20544 4 1 1154 2570 yes 269593 21 1 2570 855 no 69743 22 1 855 560 yes 67087 22 2 560 4641 yes 70673 50 2 4641 579 yes 56036 4 1 579 70 no 18201 3 1 70 703 no 230025 3 1 703 1370 no 66625 9 1 1370 3292 yes 73469 66 4 3292 2908 no 230125 5 1 2908 2027 yes 107684 10 2 2027 751 yes 16600 17 1 751 1275 yes 19266 58 2 1275 1862 yes 18028 246 6 1862 746 yes 68268 16 1 746 5116 yes 108079 16 1 5116 402 no 106564 2 1 402 1575 no 83557 21 1 1575 1934 yes 27224 7 1 1934 1335 no 13842 13 1 1335 1001 yes 230848 3 1 1001 97 yes 12540 4 1 97 855 no 69743 22 1 855 4641 no 70673 50 2 4641 1592 no 20481 28 1 1592 63 no 20346 45 3 63 944 yes 231070 13 1 944 57 no 13799 21 1 57 2284 yes 16527 8 1 2284 597 yes 14284 26 1 597 622 yes 19822 4 1 622 1028 yes 231207 98 4 1028 694 yes 19664 45 6 694 286 no 67249 8 1 286 1262 yes 54216 8 1 1262 344 no 77569 20 1 344 2564 no 320827 13 2 2564 89 no 15891 3 1 89 505 yes 231549 8 2 505 1711 no 17765 17 1 1711 2610 yes 69587 16 1 2610 476 yes 209683 9 1 476 861 no 21386 12 2 861 670 no 93897 1 1 670 235 no 140904 16 2 235 403 yes 66114 1 1 403 357 yes 74198 6 1 357 682 no 80752 2 1 682 1149 yes 77053 6 1 1149 2106 yes 17135 8 1 2106 355 no 320365 4 1 355 2233 yes 100710 12 1 2233 927 yes 70797 18 2 927 127 yes 68770 13 1 127 1289 no 20817 21 1 1289 108 no 18196 6 1 108 1742 no 245945 57 6 1742 438 no 243043 10 1 438 56 yes 67980 6 1 56 316 yes 72313 10 1 316 395 yes 23881 65 10 395 1717 yes 231506 4 2 1717 298 yes 14020 15 1 298 1264 no 12889 4 1 1264 2748 no 26431 30 3 2748 29 yes 252972 10 1 29 596 yes 11938 14 1 596 1654 yes 19679 12 1 1654 5306 yes 243272 27 2 5306 2835 no 75788 34 2 2835 1294 yes 243362 36 2 1294 172 yes 12843 9 1 172 5886 yes 243725 20 1 5886 730 no 114142 102 2 730 742 no 16508 6 1 742 64 yes 18181 12 2 64 2390 no 76788 16 1 2390 2188 yes 109624 8 1 2188 111 no 243764 2 1 111 4099 yes 78937 18 1 4099 1288 no 14461 7 1 1288 362 yes 23945 18 3 362 624 no 320265 7 1 624 1491 yes 17342 54 3 1491 359 yes 16438 4 1 359 3604 yes 192193 12 1 3604 874 no 108073 6 1 874 281 no 72895 7 1 281 1237 no 232333 25 2 1237 2208 no 20965 14 2 2208 1781 yes 71779 10 1 1781 1520 yes 67602 5 1 1520 325 no 19277 16 4 325 140 no 64450 8 1 140 146 yes 73178 13 1 146 734 yes 319832 6 1 734 28 no 192198 11 1 28 2204 no 83922 7 2 2204 547 yes 208647 2 1 547 5896 no 109880 38 2 5896 1578 yes 243547 7 1 1578 4708 yes 108655 87 3 4708 152 yes 330401 25 1 152 1254 no 12288 56 4 1254 551 yes 14789 1 1 551 1492 no 16485 28 1 1492 714 no 12515 6 2 714 1294 yes 13860 14 1 1294 65 no 67456 5 1 65 550 no 71722 30 3 550 428 yes 170742 3 1 428 946 yes 12606 14 1 946 1166 no 52428 8 1 1166 86 yes 12036 12 3 86 177 no 140919 5 1 177 306 yes 15204 3 1 306 687 yes 233406 2 1 687 1255 no 116904 5 1 1255 1680 no 269959 12 1 1680 39 yes 50490 8 2 39 4095 no 22141 15 1 4095 289 yes 11535 6 1 289 7946 yes 21676 117 6 7946 2600 no 233812 26 2 2600 312 yes 19647 10 1 312 1470 no 104175 10 1 1470 33 yes 57752 18 3 33 1181 yes 101476 5 1 1181 162 no 15373 2 1 162 431 yes 232807 5 1 431 1043 no 12315 8 1 1043 591 yes 67224 2 1 591 416 yes 56632 21 3 416 1142 no 66412 10 1 1142 375 yes 12877 12 1 375 1398 no 1.01E+08 3 1 1398 389 yes 13690 48 4 389 30 yes 50781 6 1 30 7946 no 21676 117 6 7946 536 yes 319622 12 1 536 841 no 18020 4 1 841 1933 no 627214 17 1 1933 764 no 57754 3 1 764 158 yes 12577 8 2 158 3598 yes 68904 34 2 3598 1255 yes 78560 13 1 1255 512 no 52065 17 1 512 564 yes 234267 10 1 564 118 no 15111 6 1 118 214 yes 16598 2 1 214 3341 yes 622675 22 1 3341 2855 yes 73945 16 1 2855 463 yes 19724 6 1 463 125 yes 382030 5 1 125 30 yes 214627 48 3 30 2378 no 109151 22 1 2378 672 yes 19651 5 1 672 1422 yes 68051 9 2 1422 270 no 66369 2 1 270 27 no 15118 16 1 27 6737 yes 54446 104 2 6737 1587 no 66894 3 1 1587 2920 yes 11906 27 1 2920 3589 yes 244650 23 2 3589 358 yes 234734 2 1 358 32 no 93742 7 1 32 2672 no 94109 17 1 2672 59 yes 54384 1 1 59 372 yes 102141 3 1 372 88 yes 69260 7 1 88 343 yes 382014 7 1 343 412 no 15245 19 1 412 3758 yes 52335 26 1 3758 1804 yes 12398 63 3 1804 32 no 93742 7 1 32 282 yes 72826 13 1 282 217 yes 75747 1 1 217 873 yes 67398 8 1 873 2877 no 58235 16 1 2877 526 no 114873 3 1 526 934 no 235323 4 1 934 972 yes 20320 11 1 972 926 no 71973 7 1 926 509 yes 11487 20 2 509 2616 no 319758 19 1 2616 3339 no 59046 44 2 3339 1409 yes 17918 12 1 1409 337 yes 76477 1 1 337 860 yes 211586 96 6 860 113 no 13813 6 2 113 354 no 54214 2 1 354 4528 no 57246 9 1 4528 63 yes 80517 4 1 63 34 no 235283 1 1 34 936 no 72828 2 1 936 89 yes 20660 2 1 89 667 no 192663 7 1 667 2630 no 330941 16 1 2630 1262 yes 244895 22 1 1262 2536 yes 93683 19 1 2536 405 no 207667 36 4 405 199 no 17130 6 1 199 3103 yes 235442 18 1 3103 1237 no 83603 6 2 1237 999 yes 108837 2 1 999 1384 no 20616 8 1 1384 1296 yes 192287 6 1 1296 1080 yes 74769 3 1 1080 87 no 108068 2 1 87 3829 no 12217 23 1 3829 1812 yes 270201 12 1 1812 1308 yes 69035 9 1 1308 1438 yes 13205 41 1 1438 564 yes 18555 8 2 564 76 yes 74365 16 1 76 121 no 53623 14 1 121 1739 yes 14265 21 1 1739 1130 yes 12111 2 1 1130 946 no 236899 24 2 946 3150 yes 11977 34 2 3150 890 no 245595 9 1 890 110 yes 67117 4 1 110 1028 yes 12361 36 1 1028 444 yes 72018 2 1 444 1927 yes 14396 3 1 1927 328 no 17524 4 1 328 574 yes 22589 11 1 574 5908 no 13193 124 4 5908 605 no 70771 3 1 605 1260 yes 26900 18 1 1260

targetseed regulation 8mer downregulation 8mer downregulation 8mer upregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-m8 upregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 7mer-1a upregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 8mer upregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 8mer downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer upregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 upregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer upregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 8mer upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-m8 upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 8mer upregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 8mer upregulation 7mer-m8 upregulation 8mer downregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 8mer upregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-m8 upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 upregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 8mer downregulation targetseed regulation 8mer downregulation 8mer downregulation 8mer upregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 8mer downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 8mer upregulation 7mer-1a upregulation 8mer downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 upregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer upregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer upregulation 8mer upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 8mer upregulation 8mer upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a upregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 8mer downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 7mer-1a upregulation 7mer-m8 upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a upregulation 8mer downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 upregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 7mer-1a upregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer upregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 8mer downregulation 8mer upregulation 8mer upregulation 7mer-m8 upregulation 8mer downregulation 8mer upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-1a upregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-1a upregulation 8mer downregulation 7mer-1a upregulation 7mer-1a upregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 upregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-m8 upregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a upregulation 8mer upregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer upregulation 7mer-m8 upregulation 7mer-m8 downregulation 8mer upregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-m8 downregulation 7mer-1a downregulation 8mer upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer upregulation 8mer upregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 upregulation 7mer-1a downregulation 7mer-1a downregulation 7mer-1a upregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-m8 downregulation 8mer upregulation 8mer downregulation 7mer-1a downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 upregulation 7mer-m8 upregulation 8mer downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 7mer-1a upregulation 7mer-m8 upregulation 7mer-m8 upregulation 7mer-1a downregulation 8mer downregulation 7mer-1a upregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a upregulation 8mer downregulation 7mer-m8 downregulation 8mer downregulation 7mer-m8 downregulation 7mer-1a downregulation 7mer-m8 downregulation 8mer downregulation 8mer downregulation 7mer-1a downregulation 7mer-m8 upregulation 8mer downregulation