Xu Shun, Huang Haijiao, Li Nanhong, Zhang Bing, Jia Yubin, Yang Yukun, Yuan Yuan, Xiong Xing-Dong, Wang Dengchuan, Zheng Hui-Ling, Liu Xinguang
Institute of Aging Research, Guangdong Medical University, Dongguan, PR China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, PR China; Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, PR China.
Institute of Aging Research, Guangdong Medical University, Dongguan, PR China; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, PR China; Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, PR China.
Biochem Biophys Res Commun. 2016 May 13;473(4):1064-1070. doi: 10.1016/j.bbrc.2016.04.016. Epub 2016 Apr 6.
MicroRNAs are a large class of tiny noncoding RNAs, which have emerged as critical regulators of gene expression, and thus are involved in multiple cellular processes, including cellular senescence. MicroRNA-33 has previously been established to exert crucial effect on cell proliferation, lipid metabolism and cholesterol metabolism. Nonetheless, the association between microRNA-33 and cellular senescence and its underlying molecular mechanism are far to be elucidated. The present study has attempted to probe into the effect of microRNA-33 on MEFs senescence. Our data unveiled that microRNA-33 was dramatically down-regulated in senescent MEFs compared to the young MEFs, and ectopic expression of microRNA-33 promoted MEFs senescence, while knock-down of microRNA-33 exhibited a protective effect against senescence phenotype. Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse. Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33. Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression.
微小RNA是一大类微小的非编码RNA，已成为基因表达的关键调节因子，因此参与包括细胞衰老在内的多种细胞过程。先前已证实微小RNA - 33对细胞增殖、脂质代谢和胆固醇代谢发挥关键作用。然而，微小RNA - 33与细胞衰老之间的关联及其潜在分子机制仍有待阐明。本研究试图探究微小RNA - 33对小鼠胚胎成纤维细胞（MEFs）衰老的影响。我们的数据表明，与年轻的MEFs相比，衰老的MEFs中微小RNA - 33显著下调，微小RNA - 33的异位表达促进了MEFs衰老，而敲低微小RNA - 33则对衰老表型具有保护作用。此外，我们在小鼠中验证了细胞周期蛋白依赖性激酶6（CDK6）是微小RNA - 33的直接靶点。沉默CDK6与微小RNA - 33类似地诱导了MEFs的早衰表型，而强制表达CDK6则显著逆转了微小RNA - 33的衰老诱导作用。综上所述，我们的结果表明微小RNA - 33可能通过抑制CDK6表达来增强MEFs的复制性衰老。
