CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity

iScience

Marie Robert¹  Jebrane Bouaoud²  Pierre Saintigny²  Gabriel Ichim²  Alain Viari²  Vincent Lavergne³  Marco A. Mendoza-Parra⁴  Jean-Philippe Foy⁵  Hinrich Gronemeyer⁶  Benjamin Gibert⁶  Alain Puisieux⁶  Maha Siouda⁶  Laurie Tonon⁶  Serge N. Manie⁶  Peter Mulligan⁶  Maria Ouzounova⁶  Audrey D. Dujardin⁶  Laetitia Barbollat-Boutrand⁶ 

[1] Department of Maxillo-facial Surgery and Stomatology, Pitié-Salpétrière Hospital, Pierre et Marie Curie University Paris 6, Sorbonne Paris Cite University, AP-HP, Paris 75013, France;Equipe Labellisée Ligue Contre le Cancer, LabEx DEVweCAN;INRIA Grenoble-Rhône-Alpes, 655 Avenue de l’Europe, Montbonnot-Saint-Martin 38330, France;Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U964, University of Strasbourg, Illkirch, France;Synergie Lyon Cancer, Plateforme de Bioinformatique “Gilles Thomas”, Centre Léon Bérard, 28 rue Lannec, Lyon 69008, France;Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Lyon, France;

关键词: Molecular Mechanism of Gene Regulation;    Stem Cells Research;    Functional Aspects of Cell Biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression but remains poorly understood. We found that the uncharacterized epigenetic factor chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition. CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-κB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1 and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-κB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.

【 授权许可】

Unknown