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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. -- Highlights: •MicroRNA-33 was dramatically down-regulated in senescent MEF cells. •Altered expression of microRNA-33 exerted a critical role in MEFs senescence. •MicroRNA-33 promoted the replicative senescence of MEFs via targeting ofmore » CDK6.« less

Authors:
; ; ; ; ; ; ; ; ;  [1];  [1]
  1. Institute of Aging Research, Guangdong Medical University, Dongguan (China)
Publication Date:
OSTI Identifier:
22598714
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 473; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; CHOLESTEROL; FIBROBLASTS; GALACTOSIDASE; GENES; LIPIDS; METABOLISM; MICE; PHENOTYPE; RNA

Citation Formats

Xu, Shun, Huang, Haijiao, Li, Nanhong, Zhang, Bing, Jia, Yubin, Yang, Yukun, Yuan, Yuan, Xiong, Xing-dong, Wang, Dengchuan, Zheng, Hui-ling, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, Liu, Xinguang, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, and Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang. MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.04.016.
Xu, Shun, Huang, Haijiao, Li, Nanhong, Zhang, Bing, Jia, Yubin, Yang, Yukun, Yuan, Yuan, Xiong, Xing-dong, Wang, Dengchuan, Zheng, Hui-ling, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, Liu, Xinguang, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, & Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang. MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6. United States. doi:10.1016/J.BBRC.2016.04.016.
Xu, Shun, Huang, Haijiao, Li, Nanhong, Zhang, Bing, Jia, Yubin, Yang, Yukun, Yuan, Yuan, Xiong, Xing-dong, Wang, Dengchuan, Zheng, Hui-ling, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, Liu, Xinguang, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan, and Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang. Fri . "MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6". United States. doi:10.1016/J.BBRC.2016.04.016.
@article{osti_22598714,
title = {MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6},
author = {Xu, Shun and Huang, Haijiao and Li, Nanhong and Zhang, Bing and Jia, Yubin and Yang, Yukun and Yuan, Yuan and Xiong, Xing-dong and Wang, Dengchuan and Zheng, Hui-ling and Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan and Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang and Liu, Xinguang and Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan and Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang},
abstractNote = {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. -- Highlights: •MicroRNA-33 was dramatically down-regulated in senescent MEF cells. •Altered expression of microRNA-33 exerted a critical role in MEFs senescence. •MicroRNA-33 promoted the replicative senescence of MEFs via targeting of CDK6.},
doi = {10.1016/J.BBRC.2016.04.016},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 473,
place = {United States},
year = {2016},
month = {5}
}