Variations in Microrna-25 Expression Influence the Severity of Diabetic
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Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002) -
The Oestrogen Receptor Alpha-Regulated Lncrna NEAT1 Is a Critical Modulator of Prostate Cancer
ARTICLE Received 5 Dec 2013 | Accepted 26 Sep 2014 | Published 21 Nov 2014 DOI: 10.1038/ncomms6383 OPEN The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer Dimple Chakravarty1,2, Andrea Sboner1,2,3, Sujit S. Nair4, Eugenia Giannopoulou5,6, Ruohan Li7, Sven Hennig8, Juan Miguel Mosquera1,2, Jonathan Pauwels1, Kyung Park1, Myriam Kossai1,2, Theresa Y. MacDonald1, Jacqueline Fontugne1,2, Nicholas Erho9, Ismael A. Vergara9, Mercedeh Ghadessi9, Elai Davicioni9, Robert B. Jenkins10, Nallasivam Palanisamy11,12, Zhengming Chen13, Shinichi Nakagawa14, Tetsuro Hirose15, Neil H. Bander16, Himisha Beltran1,2, Archa H. Fox7, Olivier Elemento2,3 & Mark A. Rubin1,2 The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERa)is expressed in prostate cancers, independent of AR status. However, the role of ERa remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERa-specific non-coding transcriptome signature. Among putatively ERa-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is asso- ciated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. 1 Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 413 East 69th Street, Room 1402, New York, New York 10021, USA. -
Inhibition of Single Minded 2 Gene Expression Mediates Tumor-Selective Apoptosis and Differentiation in Human Colon Cancer Cells
Inhibition of Single Minded 2 gene expression mediates tumor-selective apoptosis and differentiation in human colon cancer cells Mireille J. Aleman*†‡§, Maurice Phil DeYoung*†§¶, Matthew Tress*†, Patricia Keating*†, Gary W. Perryʈ, and Ramaswamy Narayanan*†** *Center for Molecular Biology and Biotechnology, Departments of †Biology and ‡Chemistry, and ¶Center for Complex System and Brain Sciences, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431 Communicated by Herbert Weissbach, Florida Atlantic University, Boca Raton, FL, July 21, 2005 (received for review April 4, 2005) A Down’s syndrome associated gene, Single Minded 2 gene short bound AhR͞ARNT complex (12) and hence prevent carcinogen form (SIM2-s), is specifically expressed in colon tumors but not in metabolism, leading to cumulative DNA damage and cancer. the normal colon. Antisense inhibition of SIM2-s in a RKO-derived The growth arrest and DNA damage (GADD) family of genes colon carcinoma cell line causes growth inhibition, apoptosis, and was originally isolated from UV radiation-treated cells and subse- inhibition of tumor growth in a nude mouse tumoriginicity model. quently grouped according to their coordinate regulation by growth The mechanism of cell death in tumor cells is unclear. In the present arrest and DNA damage (13). The GADD family members include study, we investigated the pathways underlying apoptosis. Apo- GADD34,-45␣,-45,-45␥, and -153 (14, 15). These are stress- ptosis was seen in a tumor cell-specific manner in RKO cells but not response genes induced by both genotoxic and nongenotoxic in normal renal epithelial cells, despite inhibition of SIM2-s expres- stresses (16–18). GADD45␣ is the most extensively studied mem- sion in both of these cells by the antisense. -
(P -Value<0.05, Fold Change≥1.4), 4 Vs. 0 Gy Irradiation
Table S1: Significant differentially expressed genes (P -Value<0.05, Fold Change≥1.4), 4 vs. 0 Gy irradiation Genbank Fold Change P -Value Gene Symbol Description Accession Q9F8M7_CARHY (Q9F8M7) DTDP-glucose 4,6-dehydratase (Fragment), partial (9%) 6.70 0.017399678 THC2699065 [THC2719287] 5.53 0.003379195 BC013657 BC013657 Homo sapiens cDNA clone IMAGE:4152983, partial cds. [BC013657] 5.10 0.024641735 THC2750781 Ciliary dynein heavy chain 5 (Axonemal beta dynein heavy chain 5) (HL1). 4.07 0.04353262 DNAH5 [Source:Uniprot/SWISSPROT;Acc:Q8TE73] [ENST00000382416] 3.81 0.002855909 NM_145263 SPATA18 Homo sapiens spermatogenesis associated 18 homolog (rat) (SPATA18), mRNA [NM_145263] AA418814 zw01a02.s1 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE:767978 3', 3.69 0.03203913 AA418814 AA418814 mRNA sequence [AA418814] AL356953 leucine-rich repeat-containing G protein-coupled receptor 6 {Homo sapiens} (exp=0; 3.63 0.0277936 THC2705989 wgp=1; cg=0), partial (4%) [THC2752981] AA484677 ne64a07.s1 NCI_CGAP_Alv1 Homo sapiens cDNA clone IMAGE:909012, mRNA 3.63 0.027098073 AA484677 AA484677 sequence [AA484677] oe06h09.s1 NCI_CGAP_Ov2 Homo sapiens cDNA clone IMAGE:1385153, mRNA sequence 3.48 0.04468495 AA837799 AA837799 [AA837799] Homo sapiens hypothetical protein LOC340109, mRNA (cDNA clone IMAGE:5578073), partial 3.27 0.031178378 BC039509 LOC643401 cds. [BC039509] Homo sapiens Fas (TNF receptor superfamily, member 6) (FAS), transcript variant 1, mRNA 3.24 0.022156298 NM_000043 FAS [NM_000043] 3.20 0.021043295 A_32_P125056 BF803942 CM2-CI0135-021100-477-g08 CI0135 Homo sapiens cDNA, mRNA sequence 3.04 0.043389246 BF803942 BF803942 [BF803942] 3.03 0.002430239 NM_015920 RPS27L Homo sapiens ribosomal protein S27-like (RPS27L), mRNA [NM_015920] Homo sapiens tumor necrosis factor receptor superfamily, member 10c, decoy without an 2.98 0.021202829 NM_003841 TNFRSF10C intracellular domain (TNFRSF10C), mRNA [NM_003841] 2.97 0.03243901 AB002384 C6orf32 Homo sapiens mRNA for KIAA0386 gene, partial cds. -
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NEUROSCIENCE RESEARCH NOTES OPEN ACCESS | RESEARCH NOTES ISSN: 2576-828X Transcriptomic profiling of skeletal muscle from the Ts1Cje mouse model of Down syndrome suggests dysregulation of trisomic genes associated with neuromuscular junction signaling, oxidative stress and chronic inflammation Melody Pui Yee Leong 1,2, Usman Bala 2,3, Chai Ling Lim 2,3, Rozita Rosli 1,2, Pike-See Cheah 2,3 and King-Hwa Ling 1,2,* 1 Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. 2 Genetics and Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. 3 Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. * Correspondence: [email protected]; Tel.: +603-8947 2564 Received: 10 May 2018; Accepted: 21 August 2018; Published: 27 August 2018 Edited by: Azlina Ahmad Annuar (University of Malaya, Malaysia) Reviewed by: Ruth Chia (National Institute on Aging, National Institutes of Health, USA); Shelisa Tey (Institute of Neuropathology, RWTH University Hospital Aachen, Germany) DOI: https://doi.org/10.31117/neuroscirn.v1i1.12 Abstract: Ts1Cje is a mouse model of Down syndrome (DS) with partial triplication of chromosome 16, which encompasses a high number of human chromosome 21 (HSA21) orthologous genes. The mouse model exhibits muscle weakness resembling hypotonia in DS individuals. The effect of extra gene dosages on muscle weakness or hypotonia in Ts1Cje and DS individuals remains unknown. To identify molecular dysregulation of the skeletal muscle, we compared the transcriptomic signatures of soleus and extensor digitorum longus (EDL) muscles between the adult Ts1Cje and disomic littermates. -
The Nuclear Hormone Receptor Coactivator SRC-1 Is a Specific Target of P300 TSO-PANG YAO, GREGORY Ku, NAIDONG ZHOU, RALPH SCULLY, and DAVID M
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 10626-10631, October 1996 Biochemistry The nuclear hormone receptor coactivator SRC-1 is a specific target of p300 TSO-PANG YAO, GREGORY Ku, NAIDONG ZHOU, RALPH SCULLY, AND DAVID M. LIvINGSTON* Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115 Contributed by David M. Livingston, June 17, 1996 ABSTRACT p300 and its family member, CREB-binding derlying ligand activation of nuclear receptor transcription protein (CBP), function as key transcriptional coactivators by activity. virtue of their interaction with the activated forms of certain Specifically, it has been shown that, upon ligand binding, a transcription factors. In a search for additional cellular specific set of proteins are recruited to the hormone bound targets of p300/CBP, a protein-protein cloning strategy, (i.e., activated) receptor (11-13). It was hypothesized that surprisingly identified SRC-1, a coactivator involved in nu- these multiprotein complexes assemble and become transcrip- clear hormone receptor transcriptional activity, as a p300/ tionally active in response to hormone binding. Identifying and CBP interactive protein. p300 and SRC-1 interact, specifically, understanding how individual components of these complexes in vitro and they also form complexes in vivo. Moreover, we function are part of the key to understand how nuclear show that SRC-1 encodes a new member of the basic helix- receptors modulate transcription. Recently, one of the nuclear loop-helix-PAS domain family and that it physically interacts receptor-binding proteins, steroid receptor coactivator-1 with the retinoic acid receptor in response to hormone bind- (SRC-1), was identified and cloned. -
Genetic Testing for Acute Myeloid Leukemia AHS-M2062
Corporate Medical Policy Genetic Testing for Acute Myeloid Leukemia AHS-M2062 File Name: genetic_testing_for_acute_myeloid_leukemia Origination: 1/1/2019 Last CAP Review: 8/2021 Next CAP Review: 8/2022 Last Review: 8/2021 Description of Procedure or Service Acute myeloid leukemia (AML) is characterized by large numbers of abnormal, immature myeloid cells in the bone marrow and peripheral blood resulting from genetic changes in hematopoietic precursor cells which disrupt normal hematopoietic growth and differentiation (Stock, 2020). Related Policies: Genetic Cancer Susceptibility Using Next Generation Sequencing AHS-M2066 Molecular Panel Testing of Cancers to Identify Targeted Therapy AHS-M2109 Serum Tumor Markers for Malignancies AHS-G2124 Minimal Residual Disease (MRD) AHS- M2175 ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for genetic testing for acute myeloid leukemia when it is determined to be medically necessary because the medical criteria and guidelines shown below are met. Benefits Application This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy. When Genetic Testing for Acute Myeloid Leukemia is covered The use of genetic testing for acute myeloid leukemia is considered medically necessary for the following: A. Genetic testing for FLT3 internal tandem duplication and tyrosine kinase domain mutations (ITD and TKD), IDH1, IDH2, TET2, WT1, DNMT3A, ASXL1 and/or TP53 in adult and pediatric patients with suspected or confirmed AML of any type for prognostic and/or therapeutic purposes. -
Application of Microrna Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease
Article Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease Jennifer L. Major, Rushita A. Bagchi * and Julie Pires da Silva * Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; [email protected] * Correspondence: [email protected] (R.A.B.); [email protected] (J.P.d.S.) Supplementary Tables Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 www.mdpi.com/journal/mps Methods Protoc. 2021, 4, 5. https://doi.org/10.3390/mps4010005 2 of 25 Table 1. List of all hsa-miRs identified by Human microRNA Disease Database (HMDD; v3.2) analysis. hsa-miRs were identified using the term “genetics” and “circulating” as input in HMDD. Targets CAD hsa-miR-1 Targets IR injury hsa-miR-423 Targets Obesity hsa-miR-499 hsa-miR-146a Circulating Obesity Genetics CAD hsa-miR-423 hsa-miR-146a Circulating CAD hsa-miR-149 hsa-miR-499 Circulating IR Injury hsa-miR-146a Circulating Obesity hsa-miR-122 Genetics Stroke Circulating CAD hsa-miR-122 Circulating Stroke hsa-miR-122 Genetics Obesity Circulating Stroke hsa-miR-26b hsa-miR-17 hsa-miR-223 Targets CAD hsa-miR-340 hsa-miR-34a hsa-miR-92a hsa-miR-126 Circulating Obesity Targets IR injury hsa-miR-21 hsa-miR-423 hsa-miR-126 hsa-miR-143 Targets Obesity hsa-miR-21 hsa-miR-223 hsa-miR-34a hsa-miR-17 Targets CAD hsa-miR-223 hsa-miR-92a hsa-miR-126 Targets IR injury hsa-miR-155 hsa-miR-21 Circulating CAD hsa-miR-126 hsa-miR-145 hsa-miR-21 Targets Obesity hsa-mir-223 hsa-mir-499 hsa-mir-574 Targets IR injury hsa-mir-21 Circulating IR injury Targets Obesity hsa-mir-21 Targets CAD hsa-mir-22 hsa-mir-133a Targets IR injury hsa-mir-155 hsa-mir-21 Circulating Stroke hsa-mir-145 hsa-mir-146b Targets Obesity hsa-mir-21 hsa-mir-29b Methods Protoc. -
Supplementary Materials and Tables a and B
SUPPLEMENTARY MATERIAL 1 Table A. Main characteristics of the subset of 23 AML patients studied by high-density arrays (subset A) WBC BM blasts MYST3- MLL Age/Gender WHO / FAB subtype Karyotype FLT3-ITD NPM status (x109/L) (%) CREBBP status 1 51 / F M4 NA 21 78 + - G A 2 28 / M M4 t(8;16)(p11;p13) 8 92 + - G G 3 53 / F M4 t(8;16)(p11;p13) 27 96 + NA G NA 4 24 / M PML-RARα / M3 t(15;17) 5 90 - - G G 5 52 / M PML-RARα / M3 t(15;17) 1.5 75 - - G G 6 31 / F PML-RARα / M3 t(15;17) 3.2 89 - - G G 7 23 / M RUNX1-RUNX1T1 / M2 t(8;21) 38 34 - + ND G 8 52 / M RUNX1-RUNX1T1 / M2 t(8;21) 8 68 - - ND G 9 40 / M RUNX1-RUNX1T1 / M2 t(8;21) 5.1 54 - - ND G 10 63 / M CBFβ-MYH11 / M4 inv(16) 297 80 - - ND G 11 63 / M CBFβ-MYH11 / M4 inv(16) 7 74 - - ND G 12 59 / M CBFβ-MYH11 / M0 t(16;16) 108 94 - - ND G 13 41 / F MLLT3-MLL / M5 t(9;11) 51 90 - + G R 14 38 / F M5 46, XX 36 79 - + G G 15 76 / M M4 46 XY, der(10) 21 90 - - G NA 16 59 / M M4 NA 29 59 - - M G 17 26 / M M5 46, XY 295 92 - + G G 18 62 / F M5 NA 67 88 - + M A 19 47 / F M5 del(11q23) 17 78 - + M G 20 50 / F M5 46, XX 61 59 - + M G 21 28 / F M5 46, XX 132 90 - + G G 22 30 / F AML-MD / M5 46, XX 6 79 - + M G 23 64 / M AML-MD / M1 46, XY 17 83 - + M G WBC: white blood cell. -
The Role of Npas4 in Neuroprotection and Neurogenesis
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mQBGEGR?JPCQC?PAFPCNMQGRMPW RFC-G@P?PWA?R?JMESC?LB?JQMRFPMSEFUC@ QC?PAFCLEGLCQ SLJCQQNCPKGQQGMLF?Q@CCLEP?LRCB@WRFC6LGTCPQGRWRMPCQRPGAR?AACQQDMP? NCPGMBMDRGKC 4GELCB %?RC 2:=>F;4364<4=CB *UMSJBJGICRMR?ICRFGQMNNMPRSLGRWRMCVNPCQQKWSRKMQREP?RGRSBCRMK?LWGLBGTGBS?JQUFM -
Maintenance of Mammary Epithelial Phenotype by Transcription Factor Runx1 Through Mitotic Gene Bookmarking Joshua Rose University of Vermont
University of Vermont ScholarWorks @ UVM Graduate College Dissertations and Theses Dissertations and Theses 2019 Maintenance Of Mammary Epithelial Phenotype By Transcription Factor Runx1 Through Mitotic Gene Bookmarking Joshua Rose University of Vermont Follow this and additional works at: https://scholarworks.uvm.edu/graddis Part of the Biochemistry Commons, and the Genetics and Genomics Commons Recommended Citation Rose, Joshua, "Maintenance Of Mammary Epithelial Phenotype By Transcription Factor Runx1 Through Mitotic Gene Bookmarking" (2019). Graduate College Dissertations and Theses. 998. https://scholarworks.uvm.edu/graddis/998 This Thesis is brought to you for free and open access by the Dissertations and Theses at ScholarWorks @ UVM. It has been accepted for inclusion in Graduate College Dissertations and Theses by an authorized administrator of ScholarWorks @ UVM. For more information, please contact [email protected]. MAINTENANCE OF MAMMARY EPITHELIAL PHENOTYPE BY TRANSCRIPTION FACTOR RUNX1 THROUGH MITOTIC GENE BOOKMARKING A Thesis Presented by Joshua Rose to The Faculty of the Graduate College of The University of Vermont In Partial Fulfillment of the Requirements for the Degree of Master of Science Specializing in Cellular, Molecular, and Biomedical Sciences January, 2019 Defense Date: November 12, 2018 Thesis Examination Committee: Sayyed Kaleem Zaidi, Ph.D., Advisor Gary Stein, Ph.D., Advisor Seth Frietze, Ph.D., Chairperson Janet Stein, Ph.D. Jonathan Gordon, Ph.D. Cynthia J. Forehand, Ph.D. Dean of the Graduate College ABSTRACT Breast cancer arises from a series of acquired mutations that disrupt normal mammary epithelial homeostasis and create multi-potent cancer stem cells that can differentiate into clinically distinct breast cancer subtypes. Despite improved therapies and advances in early detection, breast cancer remains the leading diagnosed cancer in women. -
Ohnologs in the Human Genome Are Dosage Balanced and Frequently Associated with Disease
Ohnologs in the human genome are dosage balanced and frequently associated with disease Takashi Makino1 and Aoife McLysaght2 Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland Edited by Michael Freeling, University of California, Berkeley, CA, and approved April 9, 2010 (received for review December 21, 2009) About 30% of protein-coding genes in the human genome are been duplicated by WGD, subsequent loss of individual genes related through two whole genome duplication (WGD) events. would result in a dosage imbalance due to insufficient gene Although WGD is often credited with great evolutionary impor- product, thus leading to biased retention of dosage-balanced tance, the processes governing the retention of these genes and ohnologs. In fact, evidence for preferential retention of dosage- their biological significance remain unclear. One increasingly pop- balanced genes after WGD is accumulating (4, 7, 11–20). Copy ular hypothesis is that dosage balance constraints are a major number variation [copy number polymorphism (CNV)] describes determinant of duplicate gene retention. We test this hypothesis population level polymorphism of small segmental duplications and show that WGD-duplicated genes (ohnologs) have rarely and is known to directly correlate with gene expression levels (21– experienced subsequent small-scale duplication (SSD) and are also 24). Thus, CNV of dosage-balanced genes is also expected to be refractory to copy number variation (CNV) in human populations deleterious. This model predicts that retained ohnologs should be and are thus likely to be sensitive to relative quantities (i.e., they are enriched for dosage-balanced genes that are resistant to sub- dosage-balanced).