title: CBX7 and miR-9 are part of an autoregulatory loop controlling p16(INK) (4a).
abstract: Polycomb repressive complexes (PRC1 and PRC2) are epigenetic regulators that act in coordination to influence multiple cellular processes including pluripotency, differentiation, cancer and senescence. The role of PRCs in senescence can be mostly explained by their ability to repress the INK4/ARF locus. CBX7 is one of five mammalian orthologues of Drosophila Polycomb that forms part of PRC1. Despite the relevance of CBX7 for regulating senescence and pluripotency, we have a limited understanding of how the expression of CBX7 is regulated. Here we report that the miR-9 family of microRNAs (miRNAS) downregulates the expression of CBX7. In turn, CBX7 represses miR-9-1 and miR-9-2 as part of a regulatory negative feedback loop. The miR-9/CBX7 feedback loop is a regulatory module contributing to induction of the cyclin-dependent kinase inhibitor (CDKI) p16(INK4a) during senescence. The ability of the miR-9 family to regulate senescence could have implications for understanding the role of miR-9 in cancer and aging.
authors.affiliation: Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.|Molecular Oncology Laboratory, CRUK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.|Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: O'Loghlen
authors.affiliation: Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.|Molecular Oncology Laboratory, CRUK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Brookes
authors.affiliation: Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin
authors.affiliation: Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rapisarda
authors.affiliation: Molecular Oncology Laboratory, CRUK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Peters
authors.affiliation: Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
authors.forename: Jesús
authors.initials: J
authors.lastname: Gil
mesh_terms: D000375:Aging / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C503627:CBX7 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D063150:Polycomb Repressive Complex 1
keywords: CBX7; Polycomb; miR-9; p16INK4a; senescence