DOCSLIB.ORG

Lncrna MAFG-AS1 Promotes the Aggressiveness of Breast Carcinoma Through Regulating Mir-339-5P/MMP15

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lncrna MAFG-AS1 Promotes the Aggressiveness of Breast Carcinoma Through Regulating Mir-339-5P/MMP15 European Review for Medical and Pharmacological Sciences 2019; 23: 2838-2846 LncRNA MAFG-AS1 promotes the aggressiveness of breast carcinoma through regulating miR-339-5p/MMP15 H. LI1, G.-Y. ZHANG2, C.-H. PAN3, X.-Y. ZHANG1, X.-Y. SU4 1Department of Obstetrics and Gynecology, Shandong Jiyang Public Hospital, Ji’nan, Shandong, China 2Department of Anesthesiology, Shandong Jiyang Public Hospital, Ji’nan, Shandong, China 3Department of Obstetrics and Gynecology, LanCun central hospital, Jimo, Shandong, China 4Department of Critical Care Medicine, Tai’an Central Hospital, Tai’an, Shandong, China Abstract. – OBJECTIVE: The main purposes of and is the leading cause of cancer-related deaths this study are to investigate the possible effects worldwide1. Recently, treatment strategies, such of long noncoding RNAs (lncRNAs) MAFG-AS1 on as chemotherapy, radiotherapy and molecular tar- the growth and metastasis of breast carcinoma. PATIENTS AND METHODS: geting treatment significantly improve the thera- The quantitative 2 Real Time-Polymerase Chain Reaction (qRT- peutic outcome of patients . However, the clinical PCR) assay was used to assess the MAFG-AS1 outcome of patients with breast cancer needs to level in breast cancer tissues and cells. The improve. The metastasis of cancer cells is one ma- wound healing and transwell invasion analy- jor difficulty of overcoming the poor prognosis of sis were applied to explore the invasion and mi- breast cancer patients. The epithelial-mesenchy- gration of breast cancer cell in vitro. The ex- mal transition (EMT) process of cancer cells is a pressions of epithelial-mesenchymal transition 3,4 (EMT) related markers were determined by West- crucial step during metastasis . Therefore, inhi- ern blotting. Xenograft model and lung metasta- bition of EMT may be helpful for inhibiting breast sis model were used to assess the progression cancer cell metastasis and for improving the poor of breast carcinoma cell in vivo. clinical outcome of patients. RESULTS: The level of lncRNA MAFG-AS1 is Earlier investigations have proved that ln- higher in breast carcinoma, and the aggressive cRNAs epigenetically regulate their target genes phenotypes of breast carcinoma cell are en- and play crucial roles in the development of hanced by MAFG-AS1 transfection. Moreover, we 5-7 identify that MAFG-AS1 overexpression reduces cancers . For example, lncRNA maternally ex- the expression of miR-339-5p and miR-339-5p is pressed gene 3 (MEG3) suppresses the growth the target of MAFG-AS1 in breast carcinoma. In and metastasis of gastric cancer cell via regulat- addition, matrix metalloproteinase 15 (MMP15) is ing the p53 signaling pathway8. In colorectal can- the functional regulated gene of miR-339-5p in cer, lncRNA MAFG-AS1 promotes the develop- breast carcinoma. The aggressiveness of breast ment of tumor through regulating miR-147b and carcinoma induced by lncRNA MAFG-AS1 is activating NADH dehydrogenase (Ubiquinone) 1 weakened by the miR-339-5p. Finally, we demon- 9 strated that the development of breast carcinoma Alpha Subcomplex, 4 (NDUFA4) . MicroRNAs cell is enhanced by MAFG-AS1 in vivo. (miRNAs), which are small endogenous nucle- CONCLUSIONS: MAFG-AS1 appears to play otides, regulate the expression of target genes. an oncogene role in breast carcinoma by regu- Currently, more than 2000 miRNAs have been lating the miR-339-5p/MMP15. identified and have been proved to be related to diseases, including cancer10,11. Key Words: Breast cancer, Metastasis, MAFG-AS1, MMP15, MiR- Here, we demonstrated that MAFA-AS1 was 339-5p. over-regulated in breast cancer tissue compared to that in adjacent normal tissue. Moreover, we identified that miR-339-5p was modulated by Introduction MAFA-AS1 in breast cancer. Additionally, we verified that the aggressiveness of breast cancer Breast cancer has been recognized as one of cell was enhanced by MAFG-AS1. Functional the most common types of malignant cancers experiments demonstrated that lncRNA MAFG- 2838 Corresponding Authors: Xiao Yan Su, MD; email: [email protected] LncRNA MAFG-AS1 and breast cancer aggressiveness by regulating miR-339-5p/MMP15 AS1 facilitated the aggressiveness of breast cancer scribed by PrimeScript RT Reagent Kit and oligo through the modulation of miR-339-5p-MMP15. dT primer (TaKaRa, Dalian, Liaoning, China). The SYBR PrimeScript miRNA RT PCR kit (Ta- KaRa, Dalian, Liaoning, China) was used to de- Materials and Methods tect the level of miRNA-363. The 2(-∆∆Ct) method was adapted to the analysis of MMP15, lncRNA Breast Carcinoma Tissues and Cells MAFG-AS1, and miR-339-5p. The primer se- Breast carcinoma cells (MDA-MB-231, quences are the as following: MMP15 forward, HCC1937, MCF-7, and MDA-MB-468) and the 5’-ATGACGACCCCCAATAAAGGA-3’, and normal epithelial breast cell line, MCF-10A, were reverse, 5’-CACCGACATGGTTACCAGC-3’; obtained from Nanjing Cobioer Biotechnolo- GAPDH forward, 5′-AGGTCGGTGTGAACG- gy Co., Ltd (Nanjing, Jiangsu, China). The cells GATTTG-3′, and reverse: 5′-TGTAGACCAT- were was cultured using Dulbecco’s Modified Ea- GTAGTTGAGGTCA-3′; miR-339-5p, forward gle’s Medium (DMEM; Thermo Fisher Scientif- 5’-GGGTCCCTGTCCTCCA-3’ and reverse: ic, Waltham, MA, USA) containing 10% of FBS 5’-TGCGTGTCGTGGAGTC-3’; U6 forward, (Thermo Fisher Scientific, Waltham, MA, USA). 5’-CTCGCTTCGGCAGCACATATACT-3’, and 42 cases of breast cancer and normal tissues were reverse, 5’-ACGCTTCACGAATTTGCGT- obtained from the Tai’an Central Hospital (Tai’an, GTC-3’; MAFG-AS1 forward, 5’-ATGACGAC- Shandong, China). The experiment protocol was CCCCAATAAAGGA-3’, and reverse, 5’-CAC- approved by the Ethics Committee of the Tai’an CGACATGGTTACCAGC-3’. Central Hospital. Luciferase Reporter Gene Assay Transfections The pmirGLO Dual-Luciferase miRNA Tar- MiRNA-control inhibitor (miR-NC inhibitor), get Expression Vector was obtained from Prome- miR-339-5p inhibitor, miRNA control (miR-NC) ga (Madison, WI, USA). The wild type 3’-UTR and miR-339-5p were obtained from GeneCopoe- of MMP15 or MAFG-AS1 (wt-MMP15 or wt- ia (Guangzhou, Guangdong, China). Scramble or MAFG-AS1) was inserted into the vector. The MAFG-AS1, which was provided by GeneCopoe- mutated type 3’-UTR of MAFG-AS1 or MMP15 ia and was cloned into the pcDNA3.1 (GeneCo- (mut-MAFG-AS1 or mut-MMP15) was produced poeia). MDA-MB-231 cell was transfected with using the quikChange XL site-directed muta- miRNAs using Lipofectamine 3000 (Thermo genesis kit (Agilent Technologies, Santa Clara, Fisher Scientific, Waltham, MA, USA). CA, USA). MAFG-AS1 and miR-339-5p or miR- 339-5p and MMP15 were co-transfected into Migration Assay MDA-MB-231 cell using the Lipofectamine 3000 5 x 105 MDA-MB-231 or MCF-7 cell was seed- (Thermo Fisher Scientific, Waltham, MA, USA). ed into 6 well plates. After 24 h, a wound was The luciferase reporter assay kit (Promega, Mad- made by a 100 μl pipette tip. The picture of the ison, WI, USA) was applied to the analysis of the wound width was taken at 0 h and 48 h, respec- luciferase activity. tively. Transplanted Tumor Model Invasion Assay 100 μl MDA-MB-231 cells (2x107) were subcu- 200 μl MCF-7 or MDA-MB-231 cells (1 x 105) taneous injected subcutaneously into nude mice. were seeded in the upper chamber of the transwell The tumor size was weekly recorded and the (Corning, Shanghai, China). 600 μl medium con- tumor volumes were calculated. Volume = 0.5× tained 20% FBS was used as a chemo-attractant length × width2. After 35 days, all mice were sac- and plated into the lower chamber. After 24 h, rificed and the tumor was extracted for the sub- 4% of paraformaldehyde and 1% of crystal vio- sequent immunohistochemical staining analysis. let were used to fix and stain the invaded cells, respectively. Experimental Metastasis Model MAFG-AS1 transfected MDA-MB-231 cell Quantitative Real-time (qRT-PCR) Assay (5×10 5) was injected into BALB/c mice through RNAs were extracted with TRIzol (Thermo the tail vein. After two weeks, the mice were sac- Fisher Scientific, Waltham, MA, USA). For the rificed and lung tissues were applied for H&E analysis the level of MMP15, RNA was tran- staining. All animal experiments were approved 2839 H. Li, G.-Y. Zhang, C.-H. Pan, X.-Y. Zhang, X.-Y. Su by the Ethics Committee of Tai’an Central Hospi- higher in breast carcinoma in contrast to normal tal (Shandong, China). (Figure 1B). Meanwhile, MAFG-AS1 was dis- tinctly over-expressed in breast carcinoma cells, Statistical Analysis including MDA-MB-231, MCF-7, MDA-MB-468, Results were expressed as the Mean ± SD. The and HCC1937) than that in the normal epitheli- difference was analyzed using either two-tailed al breast cell, MCF-10A (Figure 1C). These data Student’s t-test or one-way ANOVA followed by suggested that MAFG-AS1 was up-regulated in post-hoc Dunnett’s test. p<0.05 was statistically breast carcinoma. significant. The Aggressive Phenotypes of Breast Carcinoma was Enhanced by MAFG-AS1 Results The pcDNA3.1 containing MAFG-AS1 was transfected into the MDA-MB-231 cell to raise MAFG-AS1 Is Up-regulated in Breast MAFG-AS1 level (Figure 2A). Transwell inva- Carcinoma sion and wound closure analysis were applied to The statistical analysis of dysregulation of analyze the function of MAFG-AS1 on the MDA- lncRNAs was conducted using the dataset MB-231 cell invasion and migration. We observed (GSE113851) which contained both cancer and that the migration and invasion of MDA-MB-231 normal tissues12. We found that MAFG-AS1 was cell were enhanced by the transfection of MAFG- overexpressed in breast carcinoma tissue in con- AS1 (Figure 2B-2C). At the same time, the aggres- trast to that in the normal tissue (Figure 1A). siveness of the MCF-7 cell was also promoted by Meanwhile, MAFG-AS1 in breast cancer, as MAFG-AS1 (Figure 2D-2E).
Load more

Recommended publications
  • C/EBP Creates Elite Cells for Ipsc Reprogramming by Upregulating
    ARTICLES C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4 Bruno Di Stefano1,2,8,9,10, Samuel Collombet3,8, Janus Schou Jakobsen4,5,6,8, Michael Wierer7, Jose Luis Sardina1,2, Andreas Lackner1,2,9, Ralph Stadhouders1,2, Carolina Segura-Morales1,2, Mirko Francesconi1,2, Francesco Limone1,2, Matthias Mann7, Bo Porse4,5,6, Denis Thieffry3 and Thomas Graf1,2,10 Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) is typically inefficient and has been explained by elite-cell and stochastic models. We recently reported that B cells exposed to a pulse of C/EBPα (Bα0 cells) behave as elite cells, in that they can be rapidly and efficiently reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPα post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell gene silencing and Brd4 for the activation of the pluripotency program. C/EBPα also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. Bα0 cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBPα. The ability to reprogram somatic into pluripotent cells has revolu- complex process, where multiple players synergistically establish new tionized stem cell research with major implications for almost all transcriptional networks and remove epigenetic barriers14. Among the fields of modern biology.
    [Show full text]
  • Picosecond-Hetero-FRET Microscopy to Probe Protein-Protein Interactions in Live Cells
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector 3570 Biophysical Journal Volume 83 December 2002 3570–3577 Picosecond-Hetero-FRET Microscopy to Probe Protein-Protein Interactions in Live Cells Marc Tramier,* Isabelle Gautier,* Tristan Piolot,† Sylvie Ravalet,‡ Klaus Kemnitz,† Jacques Coppey,* Christiane Durieux,* Vincent Mignotte,‡ and Maı¨te´ Coppey-Moisan* *Institut Jacques Monod, UMR 7592, CNRS, Universite´s P6/P7, 75251 Paris Cedex 05, France; †EuroPhoton GmbH, D-12247, Berlin, Germany; and ‡ICGM, Department of Hematology, Maternite´ Port-Royal, 75014 Paris, France ABSTRACT By using a novel time- and space-correlated single-photon counting detector, we show that fluorescence resonance energy transfer (FRET) between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) fused to herpes simplex virus thymidine kinase (TK) monomers can be used to reveal homodimerization of TK in the nucleus and cytoplasm of live cells. However, the quantification of energy transfer was limited by the intrinsic biexponential fluorescence decay of the donor CFP (lifetimes of 1.3 Ϯ 0.2 ns and 3.8 Ϯ 0.4 ns) and by the possibility of homodimer formation between two TK-CFP. In contrast, the heterodimerization of the transcriptional factor NF-E2 in the nucleus of live cells was quantified from the analysis of the fluorescence decays of GFP in terms of 1) FRET efficiency between GFP and DsRed chromophores fused to p45 and MafG, respectively, the two subunits of NF-E2 (which corresponds to an interchromophoric distance of 39 Ϯ 1 Å); and 2) fractions of GFP-p45 bound to DsRed-MafG (constant in the nucleus, varying in the range of 20% to 70% from cell to cell).
    [Show full text]
  • Human Small Maf Proteins Form Heterodimers with CNC Family Transcription Factors and Recognize the NF-E2 Motif
    Oncogene (1997) 14, 1901 ± 1910 1997 Stockton Press All rights reserved 0950 ± 9232/97 $12.00 Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif Tsutomu Toki1, Jugou Itoh2, Jun'ichi Kitazawa1, Koji Arai1, Koki Hatakeyama3, Jun-itsu Akasaka4, Kazuhiko Igarashi5, Nobuo Nomura6, Masaru Yokoyama1, Masayuki Yamamoto5 and Etsuro Ito1 1Department of Pediatrics, 2Medicine, School of Medicine; 3Department of Biology, Faculty of Sciences, Hirosaki University, Hirosaki 036; 4Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-77; 5Center for TARA and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305; 6Kazusa DNA Institute, Kisarazu 292, Japan The transcription factor NF-E2, a heterodimeric protein Talbot et al., 1990; Talbot and Grosveld, 1991; complex composed of p45 and small Maf family Kotkow and Orkin, 1995). Recent analyses demon- proteins, is considered crucial for the regulation of strated that NF-E2 is composed of two subunits erythroid gene expression and platelet formation. To (Andrews et al., 1993a,b; Igarashi et al., 1994). The facilitate the characterization of NF-E2 functions in large p45 subunit belongs to a family of basic leucine- human cells, we isolated cDNAs encoding two members zipper (bZip) proteins that is closely related to the of the small Maf family, MafK and MafG. The human Drosophila Cap`n'colar (the CNC family) factor mafK and mafG genes encode proteins of 156 and 162 (Mohler et al., 1991). It cannot bind to the NF-E2 amino acid residues, respectively, whose deduced amino sequence as a homodimer, but does do after forming acid sequences show approximately 95% identity to their heterodimers with chicken small Maf family proteins, respective chicken counterparts.
    [Show full text]
  • Micrornas As Modulators of Smoking-Induced Gene Expression Changes in Human Airway Epithelium
    MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium Frank Schembria,1, Sriram Sridharb,1, Catalina Perdomoc, Adam M. Gustafsond, Xiaoling Zhangd, Ayla Ergune, Jining Lua, Gang Liua, Xiaohui Zhanga, Jessica Bowersf, Cyrus Vazirib, Kristen Ottc, Kelly Sensingerf, James J. Collinse, Jerome S. Brodya, Robert Gettsf, Marc E. Lenburga,b,d, and Avrum Spiraa,b,d,2 aPulmonary Center, bDepartment of Pathology and Laboratory Medicine, and cGenetics and Genomics Graduate Program, Boston University School of Medicine, Boston, MA 02118; dBioinformatics Program, Boston University School of Engineering, Boston, MA 02215; eDepartment of Biomedical Engineering and Center for BioDynamics and Howard Hughes Medical Institute, Boston University, Boston, MA 02215; and fGenisphere, Inc., Hatfield, PA 19440 Edited by Charles R. Cantor, Sequenom Inc., San Diego, CA, and approved November 21, 2008 (received for review July 3, 2008) We have shown that smoking impacts bronchial airway gene Hundreds of human miRNAs have been cloned (11), with each of expression and that heterogeneity in this response associates with them predicted to regulate hundreds of genes by complementary smoking-related disease risk. In this study, we sought to determine binding to the 3Ј-untranslated region (UTR) of target mRNAs (12). whether microRNAs (miRNAs) play a role in regulating the airway A number of miRNAs have been shown to play important roles in gene expression response to smoking. We examined whole-ge- developmental timing, cell death, carcinogenesis, and stress responses in nome miRNA and mRNA expression in bronchial airway epithelium vitro (13–16), such as hypoxia (17). Whereas miRNA expression has and found 28 miRNAs to been examined in lung tumors (18–24), neither the expression of (20 ؍ from current and never smokers (n be differentially expressed (P < 0.05) with the majority being miRNA in bronchial epithelium nor the effect of smoking on bronchial down-regulated in smokers.
    [Show full text]
  • Metabolic Profiling of Cancer Cells Reveals Genome-Wide
    ARTICLE https://doi.org/10.1038/s41467-019-09695-9 OPEN Metabolic profiling of cancer cells reveals genome- wide crosstalk between transcriptional regulators and metabolism Karin Ortmayr 1, Sébastien Dubuis1 & Mattia Zampieri 1 Transcriptional reprogramming of cellular metabolism is a hallmark of cancer. However, systematic approaches to study the role of transcriptional regulators (TRs) in mediating 1234567890():,; cancer metabolic rewiring are missing. Here, we chart a genome-scale map of TR-metabolite associations in human cells using a combined computational-experimental framework for large-scale metabolic profiling of adherent cell lines. By integrating intracellular metabolic profiles of 54 cancer cell lines with transcriptomic and proteomic data, we unraveled a large space of associations between TRs and metabolic pathways. We found a global regulatory signature coordinating glucose- and one-carbon metabolism, suggesting that regulation of carbon metabolism in cancer may be more diverse and flexible than previously appreciated. Here, we demonstrate how this TR-metabolite map can serve as a resource to predict TRs potentially responsible for metabolic transformation in patient-derived tumor samples, opening new opportunities in understanding disease etiology, selecting therapeutic treat- ments and in designing modulators of cancer-related TRs. 1 Institute of Molecular Systems Biology, ETH Zurich, Otto-Stern-Weg 3, CH-8093 Zurich, Switzerland. Correspondence and requests for materials should be addressed to M.Z. (email: [email protected]) NATURE COMMUNICATIONS | (2019) 10:1841 | https://doi.org/10.1038/s41467-019-09695-9 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-09695-9 ranscriptional regulators (TRs) are at the interface between implemented by the additional quantification of total protein the cell’s ability to sense and respond to external stimuli or abundance and is based on the assumption that protein content T 1 changes in internal cell-state .
    [Show full text]
  • Engineered Type 1 Regulatory T Cells Designed for Clinical Use Kill Primary
    ARTICLE Acute Myeloid Leukemia Engineered type 1 regulatory T cells designed Ferrata Storti Foundation for clinical use kill primary pediatric acute myeloid leukemia cells Brandon Cieniewicz,1* Molly Javier Uyeda,1,2* Ping (Pauline) Chen,1 Ece Canan Sayitoglu,1 Jeffrey Mao-Hwa Liu,1 Grazia Andolfi,3 Katharine Greenthal,1 Alice Bertaina,1,4 Silvia Gregori,3 Rosa Bacchetta,1,4 Norman James Lacayo,1 Alma-Martina Cepika1,4# and Maria Grazia Roncarolo1,2,4# Haematologica 2021 Volume 106(10):2588-2597 1Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 2Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA; 3San Raffaele Telethon Institute for Gene Therapy, Milan, Italy and 4Center for Definitive and Curative Medicine, Stanford School of Medicine, Stanford, CA, USA *BC and MJU contributed equally as co-first authors #AMC and MGR contributed equally as co-senior authors ABSTRACT ype 1 regulatory (Tr1) T cells induced by enforced expression of interleukin-10 (LV-10) are being developed as a novel treatment for Tchemotherapy-resistant myeloid leukemias. In vivo, LV-10 cells do not cause graft-versus-host disease while mediating graft-versus-leukemia effect against adult acute myeloid leukemia (AML). Since pediatric AML (pAML) and adult AML are different on a genetic and epigenetic level, we investigate herein whether LV-10 cells also efficiently kill pAML cells. We show that the majority of primary pAML are killed by LV-10 cells, with different levels of sensitivity to killing. Transcriptionally, pAML sensitive to LV-10 killing expressed a myeloid maturation signature.
    [Show full text]
  • A MAFG-Lncrna Axis Links Systemic Nutrient Abundance to Hepatic Glucose Metabolism
    ARTICLE https://doi.org/10.1038/s41467-020-14323-y OPEN A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism Marta Pradas-Juni et al.# Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced 1234567890():,; obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse liver. Similarly, lncRNAs are lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirm that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in mouse hepatocytes and obese mice elicits a fasting-like gene expression profile, improves glucose metabolism, de-represses lncRNAs and impairs mammalian target of rapamycin (mTOR) activation. We find that obesity-repressed LincIRS2 is controlled by MAFG and observe that genetic and RNAi-mediated LincIRS2 loss causes elevated blood glucose, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease. #A full list of authors and their affiliations appears at the end of the paper. NATURE COMMUNICATIONS | (2020) 11:644 | https://doi.org/10.1038/s41467-020-14323-y | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-14323-y ellular and organism-level energy homeostasis and nutri- by MAFG and CRISPR–Cas9-mediated knockout, or antisense- Cent partitioning are instrumental for survival. In higher mediated RNA interference of LincIRS2 causes hyperglycemia, organisms, multi-organ systems evolved to react to shifts insulin resistance, likely caused by alterations in glucogenic in energy supply by storing (anabolic) or metabolizing (catabolic) gene expression in lean mice.
    [Show full text]
  • The Cataract-Linked RNA-Binding Protein Celf1 Post-Transcriptionally
    The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription factors Pax6 and Prox1 in lens development Sandeep Aryal, Justine Viet, Bailey a T Weatherbee, Archana D. Siddam, Francisco José García-Hernández, Carole Gautier-Courteille, Luc Paillard, Salil A. Lachke To cite this version: Sandeep Aryal, Justine Viet, Bailey a T Weatherbee, Archana D. Siddam, Francisco José García- Hernández, et al.. The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription factors Pax6 and Prox1 in lens development. Human Genetics, Springer Verlag, 2020, 139 (12), pp.1541-1554. 10.1007/s00439-020- 02195-7. hal-02888615 HAL Id: hal-02888615 https://hal.archives-ouvertes.fr/hal-02888615 Submitted on 10 Jul 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription
    [Show full text]
  • MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma Through a Sox9-Mediated Positive Feedback Loop
    Author Manuscript Published OnlineFirst on March 31, 2020; DOI: 10.1158/0008-5472.CAN-19-1764 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. MAFB promotes cancer stemness and tumorigenesis in osteosarcoma through a Sox9-mediated positive feedback loop Yanyan Chen1,†, Bin Wang2, †, Mengxi Huang1, †, Tao Wang 2, †, Chao Hu 3,†, Qin Liu 2, Dong Han 4, Cheng Chen1, Junliang Zhang5, Zhiping Li4, Chao Liu 6, Wenbin Lei 7,Yue Chang1, Meijuan Wu1,Dan Xiang1, Yitian Chen1, Rui Wang1, Weiqian Huang5, Zengjie Lei1 ,* and Xiaoyuan Chu1, * 1 Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, People’s Republic of China 2 Department of Gastroenterology, Daping Hospital, Third Military Medical University (Ar- my Medical University), Chongqing, People’s Republic of China 3 Department of Orthopedics, 904 Hospital of PLA, North Xingyuan Road, Beitang Dis- trict, Wuxi, Jiangsu, People’s Republic of China 4 Department of Medical Oncology, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing, Jiangsu Province, People’s Republic of China 5 Department of Orthopedics, Affiliated Jinling Hospital, Medical School of Nanjing Univer- sity, Nanjing, Jiangsu Province, People’s Republic of China 6 Department of Medical Oncology, Jinling Hospital, Nanjing Clinical School of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China 7Department of Orthopedics, Tianshui Cooperation of Chinese and Western Medicine Hospi- tal, Tianshui, Gansu Province, People’s Republic of China * To whom correspondence should be addressed. Xiaoyuan Chu, Tel: +86-25-80860131, Fax: +86-25-80860131, Email: [email protected]; Zengjie Lei, Email: leiz- [email protected] ; †The authors wish it to be known that, in their opinion, the first five authors should be regard- ed as joint First Authors.
    [Show full text]
  • C D B a Mafg Mafk Maff
    KCTD13 PROX1 IRF3 KLRG1 TJP1 COL12A1 LMBRD2 SLC25A32 TRO RASD1 HECW2 CXCR4 IRF2BPL PTPDC1 CD55 PSAT1 A MOV10L1SPRED2 TSGA10 BAIAP2 SLC1A4 TMEM39A PPAP2B BCL3 ARL4A RAPGEF1 VEGFC F3 PHLDB2 UNC5B PRDM1 LEPREL1 NR4A2 NR4A1 RAPH1 SOCS6 SULT1B1 TNFAIP3 RGS2 GIMAP1 KIAA0513 STEAP2 HSP90B1 MAP3K8 SLC25A25 TNFRSF1B DDIT4 PLEKHA1 FRMD6 C2CD4A TSPAN11 IGIP UACA RFX2 PMAIP1 IL15RA SLC2A12 MOSPD1 GIMAP6 EDN1 ADAM19 NCOA7 CLDN5 CHSY3 BCAP29 PDP1 UBE2J1 RBPMS2 PPFIBP2 KAT2B PLAU SIPA1L3 FOXN3 C14orf93 KIF26A EGR1 ACER2 MEI1 GAB1 ASUN CNN3 SIRT1 RALGPS2 PPM1H TOX2 FAM174A DNAJB4 KLF11 GBE1 CHN2 TRIM2 IL1R1 KCNJ2 TFPI2 KLF2 PPP1R3B PPARA PPP1R15B VEGFA DSE CCRN4L NR2F2 AXL EXOC8 CCNA1 B4GALT1 GIMAP7 RQCD1 ITPRIP MYADM ICAM3 FGF2 HEY1 NFIL3 CTH PTP4A3 ATP2B1 EXT1 KLHL3 KLF9 COL13A1 MID2 GDPD1 EHD3 STRBP P4HA1 OSBP2 SEC11C NFAT5 PDGFD ENC1 DUSP5 NRCAM ANO6 KLF10 SLC40A1 C2CD4B MEIS1HOXB2_ELF1 GIMAP2 SEMA6A NR4A3 KDM6B MYO1D FAM193A CSRNP2 RASGRF2 APOO ESYT2 NINL FOXP1 HDAC9 CLK1 CDK6 SCAMP5 PHLDB3 ASGR1 HELLS DIEXF SULT1C4 MBNL1 TRAF5 GIMAP8 FOXJ2_ELF1 SIX4 TEAD4_ERG ARL4C EGR3 BACH1 ITGA6 LRRC8B MFSD2A SLC4A7 RDX PLAT PODXL USF2 NR5A2 RALGAPA2 DDX60L ANGPT2 CSF1 FOXO1_ELF1 ATP1B1 CTCF P4HA3 DNAJC3 CREG1 ACRBP BRAT1 RHOBTB1 TEAD2 ARID5A FBXL2 SLC12A4 SPRY4 CDC14A ATF3 ETV5_HOXA2 CHST11 GCNT1 ESM1 FZD8 IVNS1ABP MGP CROCC SLC39A14 DUSP7 MAP2K6 TOB2 SLC35G2 SPTY2D1 BMP4 ERG ST8SIA4 POLI MCL1 SOX13 CROT CGNL1 MXD1 ETS1 THBD BACH2 ELF1 PLAUR STC1 SGK3 ITPR2 IRAK2 PHC3 FAM198B AIM1 RNF122 ETV3 FKBP14 PIM1 MX1 TNIK MMP10 ST3GAL5 DUSP1 GULP1 INPP5A PSTPIP2 MEF2C
    [Show full text]
  • Induction of Therapeutic Tissue Tolerance Foxp3 Expression Is
    Downloaded from http://www.jimmunol.org/ by guest on October 2, 2021 is online at: average * The Journal of Immunology , 13 of which you can access for free at: 2012; 189:3947-3956; Prepublished online 17 from submission to initial decision 4 weeks from acceptance to publication September 2012; doi: 10.4049/jimmunol.1200449 http://www.jimmunol.org/content/189/8/3947 Foxp3 Expression Is Required for the Induction of Therapeutic Tissue Tolerance Frederico S. Regateiro, Ye Chen, Adrian R. Kendal, Robert Hilbrands, Elizabeth Adams, Stephen P. Cobbold, Jianbo Ma, Kristian G. Andersen, Alexander G. Betz, Mindy Zhang, Shruti Madhiwalla, Bruce Roberts, Herman Waldmann, Kathleen F. Nolan and Duncan Howie J Immunol cites 35 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription http://www.jimmunol.org/content/suppl/2012/09/17/jimmunol.120044 9.DC1 This article http://www.jimmunol.org/content/189/8/3947.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of October 2, 2021.
    [Show full text]
  • Strong Binding Activity of Few Transcription Factors Is a Major Determinant of Open Chromatin
    bioRxiv preprint doi: https://doi.org/10.1101/204743; this version posted December 12, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Strong binding activity of few transcription factors is a major determinant of open chromatin Bei Wei1, Arttu Jolma1, Biswajyoti Sahu2, Lukas M. Orre3, Fan Zhong1, Fangjie Zhu1, Teemu Kivioja2, Inderpreet Kaur Sur1, Janne Lehtiö3, Minna Taipale1 and Jussi Taipale1,2,4* 1Division of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, and Department of Biosciences and Nutrition, Karolinska Institutet, SE 141 83, Stockholm, Sweden 2Genome-Scale Biology Program, P.O. Box 63, FI-00014 University of Helsinki, Finland 3Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, SE 141 83, Stockholm, Sweden 4Department of Biochemistry, University of Cambridge, United Kingdom *To whom correspondence should be addressed. E-mail: [email protected] Abstract It is well established that transcription factors (TFs) play crucial roles in determining cell identity, and that a large fraction of all TFs are expressed in most cell types. In order to globally characterize activities of TFs in cells, we have developed a novel massively parallel protein activity assay, Active TF Identification (ATI) that measures DNA-binding activity of all TFs from any species or tissue type. In contrast to previous studies based on mRNA expression or protein abundance, we found that a set of TFs binding to only around ten distinct motifs display strong DNA-binding activity in any given cell or tissue type.
    [Show full text]