Neault Mathieu, Couteau Florence, Bonneau Éric, De Guire Vincent, Mallette Frédérick A
Chromatin Structure and Cellular Senescence Research Unit, Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC, Canada; Université de Montréal, Montréal, QC, Canada.
Chromatin Structure and Cellular Senescence Research Unit, Maisonneuve-Rosemont Hospital Research Centre, Montréal, QC, Canada.
Int Rev Cell Mol Biol. 2017;334:27-98. doi: 10.1016/bs.ircmb.2017.04.001. Epub 2017 May 18.
Cellular senescence is a tumor suppressor response that acts as a barrier to cancer development and progression. In normal cells, diverse stimuli, including excessive mitogenic signaling, DNA damage or telomere shortening, trigger a senescence response characterized by stable growth arrest. Cellular senescence is orchestrated by tumor suppressor pathways, which have to be inactivated in order to impair the establishment of senescence and promote cancer. Consequently, by overcoming or bypassing this cellular response, cancer cells evade cell cycle checkpoint control leading to genomic instability and uncontrolled proliferation. MicroRNAs (MiRs) have emerged as essential factors contributing to or preventing cellular senescence. Here we detail the molecular mechanisms underlying the fine-tuning of cellular senescence signals by MiRs, and how the senescence response itself contributes to modulation of MiR expression, with a special focus on cancer and pathologies associated with aging.
细胞衰老作为一种肿瘤抑制反应,是癌症发生和发展的一道屏障。在正常细胞中,多种刺激因素,包括过度的有丝分裂信号、DNA损伤或端粒缩短,会触发以稳定生长停滞为特征的衰老反应。细胞衰老由肿瘤抑制通路精心调控,这些通路必须被失活才能削弱衰老的建立并促进癌症发生。因此,癌细胞通过克服或绕过这种细胞反应,逃避细胞周期检查点控制,导致基因组不稳定和不受控制的增殖。微小RNA(miRs)已成为促进或阻止细胞衰老的关键因素。在这里,我们详细阐述了miRs对细胞衰老信号进行微调的分子机制,以及衰老反应本身如何有助于调节miR表达,特别关注癌症和与衰老相关的病理状况。