miR‑342‑5p promotes Zmpste24‑deficient mouse embryonic fibroblasts proliferation by suppressing GAS2

Zhang,Chun‑Long; Liu,Xinguang; He,Qiu‑Jing; Zheng,Huiling; Xu,Shun; Xiong,Xing‑Dong; Yuan,Yuan; Ruan,Jie; Li,Jiang‑Bin; Xing,Yu; Zhou,Zhongjun; Deng,Shixiong

doi:10.3892/mmr.2017.7731

miR‑342‑5p promotes Zmpste24‑deficient mouse embryonic fibroblasts proliferation by suppressing GAS2

Authors:
- Chun‑Long Zhang
- Xinguang Liu
- Qiu‑Jing He
- Huiling Zheng
- Shun Xu
- Xing‑Dong Xiong
- Yuan Yuan
- Jie Ruan
- Jiang‑Bin Li
- Yu Xing
- Zhongjun Zhou
- Shixiong Deng
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Affiliations: Laboratory of Forensic Medicine and Biomedical Information, College of Basic Medical Science, Chongqing Medical University, Chongqing 400016, P.R. China, Institute of Aging Research, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China
Published online on: October 5, 2017 https://doi.org/10.3892/mmr.2017.7731
Pages: 8944-8952
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cellular senescence is an irreversible growth arrest of cells that maintain their metabolic activities. Premature senescence can be induced by different stress factors and occurs in mouse embryonic fibroblasts (MEFs) derived from Zmpste24 metalloproteinase‑deficient mice, a progeria mouse model of Hutchinson‑Gilford Progeria Syndrome. Previous studies have shown that miR‑342‑5p, an intronic microRNA (miRNA/miR) reportedly involved in ageing associated diseases, is downregulated in Zmpste24‑/‑ MEFs. However, whether miR‑342‑5p is associated with the premature senescence phenotype of Zmpste24‑/‑ MEFs remains unclear. Thus, the present study investigated the effects of miR‑342‑5p on cellular senescence and cell proliferation in Zmpste24‑/‑ MEFs. The results showed that miR‑342‑5p overexpression ameliorated the cellular senescence phenotype to a certain extent, promoted cell proliferation and increased the G2+M cell cycle phase in Zmpste24‑/‑ MEFs. Nonetheless, it was difficult to observe the opposite cell phenotypes in wild‑type (WT) MEFs transfected with the miR‑342‑5p inhibitor. Growth‑arrest‑specific 2 (GAS2) was identified as a target gene of miR‑342‑5p in Zmpste24‑/‑ MEFs. In addition, miR‑342‑5p was identified to be downregulated in WT MEFs during replicative senescence, while Gas2 was upregulated. Taken together, these findings suggest that downregulated miR‑342‑5p is involved in regulating cell proliferation and cell cycles in Zmpste24‑/‑ MEFs by suppressing GAS2 in vitro.

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