دورية أكاديمية
أعرض في EDS

PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma.

التفاصيل البيبلوغرافية
العنوان: PAX8 activates metabolic genes via enhancer elements in Renal Cell Carcinoma.
المؤلفون: Bleu M; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Gaulis S; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland.; Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland., Lopes R; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Sprouffske K; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Apfel V; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Holwerda S; Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.; Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland., Pregnolato M; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland.; Friedrich Miescher Institute for Biomedical Research and University of Basel, Basel, Switzerland., Yildiz U; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Cordoʹ V; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland.; Prinses Maxima Center for Pediatric Oncology, Utrecht, Netherlands., Dost AFM; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland.; Stem cell program, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, USA., Knehr J; Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland., Carbone W; Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland., Lohmann F; Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.; Autoimmunity, Transplantation and Inflammation, Novartis Institutes for BioMedical Research, Basel, Switzerland., Lin CY; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Bradner JE; Novartis Institutes for Biomedical Research, Cambridge, MA, USA., Kauffmann A; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Tordella L; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland., Roma G; Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland., Galli GG; Disease Area Oncology, Novartis Institute for Biomedical Research, Basel, Switzerland. giorgio.galli@novartis.com.
المصدر: Nature communications [Nat Commun] 2019 Aug 20; Vol. 10 (1), pp. 3739. Date of Electronic Publication: 2019 Aug 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Carcinoma, Renal Cell/*genetics , Ceruloplasmin/*genetics , Enhancer Elements, Genetic/*genetics , Gene Expression Regulation, Neoplastic/*genetics , Kidney Neoplasms/*genetics , PAX8 Transcription Factor/*genetics, Acetylation ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Ceruloplasmin/metabolism ; Histones/metabolism ; Humans ; Promoter Regions, Genetic/genetics ; RNA Interference ; RNA, Small Interfering/genetics
مستخلص: Transcription factor networks shape the gene expression programs responsible for normal cell identity and pathogenic state. Using Core Regulatory Circuitry analysis (CRC), we identify PAX8 as a candidate oncogene in Renal Cell Carcinoma (RCC) cells. Validation of large-scale functional genomic screens confirms that PAX8 silencing leads to decreased proliferation of RCC cell lines. Epigenomic analyses of PAX8-dependent cistrome demonstrate that PAX8 largely occupies active enhancer elements controlling genes involved in various metabolic pathways. We selected the ferroxidase Ceruloplasmin (CP) as an exemplary gene to dissect PAX8 molecular functions. PAX8 recruits histone acetylation activity at bound enhancers looping onto the CP promoter. Importantly, CP expression correlates with sensitivity to PAX8 silencing and identifies a subset of RCC cases with poor survival. Our data identifies PAX8 as a candidate oncogene in RCC and provides a potential biomarker to monitor its activity.
التعليقات: Comment in: Nat Rev Nephrol. 2019 Nov;15(11):662. (PMID: 31481715)
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معلومات مُعتمدة: R01 CA215452 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (Histones)
0 (PAX8 Transcription Factor)
0 (PAX8 protein, human)
0 (RNA, Small Interfering)
EC 1.16.3.1 (Ceruloplasmin)
تواريخ الأحداث: Date Created: 20190822 Date Completed: 20191216 Latest Revision: 20210110
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6702156
DOI: 10.1038/s41467-019-11672-1
PMID: 31431624
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-019-11672-1