title: MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6.
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.
authors.affiliation: 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.
authors.forename: Shun
authors.initials: S
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Haijiao
authors.initials: H
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Xing-Dong
authors.initials: XD
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Dengchuan
authors.initials: D
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6
keywords: CDK6; Cellular senescence; MicroRNA-33; Proliferation