CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a |
| |
| Authors: | Ana O'Loghlen Sharon Brookes Nadine Martin Valentina Rapisarda Gordon Peters Jesús Gil |
| |
| Institution: | 1. Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, London, UK;2. Molecular Oncology Laboratory, CRUK London Research Institute, London, UK;3. Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK |
| |
| 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) p16INK4a 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. |
| |
| Keywords: | CBX7 miR‐9 p16INK4a Polycomb senescence |
|
|
