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Biochem Biophys Res Commun. 2016 May 13;473(4):1064-1070. doi: 10.1016/j.bbrc.2016.04.016. Epub 2016 Apr 6.

MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6.

Author information

1
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.
2
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. Electronic address: xgliu64@126.com.

Abstract

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.

KEYWORDS:

CDK6; Cellular senescence; MicroRNA-33; Proliferation

PMID:
27059142
DOI:
10.1016/j.bbrc.2016.04.016
[Indexed for MEDLINE]

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