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.
Mol Med Rep. 2017 Dec;16(6):8944-8952. doi: 10.3892/mmr.2017.7731. Epub 2017 Oct 5.
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.
细胞衰老（cellular senescence）是一种细胞不可逆的生长停滞，其代谢活动仍得以维持。不同的应激因素可诱导细胞过早衰老（premature senescence），这种现象发生于 Zmpste24 金属蛋白酶缺陷型（Zmpste24-deficient）小鼠来源的小鼠胚胎成纤维细胞（mouse embryonic fibroblasts，MEFs）中，而后者是亨廷顿氏舞蹈病（Hutchinson-Gilford Progeria Syndrome）的一种早衰（progeria）小鼠模型。先前的研究表明，miR-342-5p 是一种与衰老相关疾病有关的内含子 miRNA（microRNA/miRNA），其在 Zmpste24-/- MEFs 中表达下调。然而，miR-342-5p 是否与 Zmpste24-/- MEFs 的过早衰老表型有关仍不清楚。因此，本研究旨在探讨 miR-342-5p 对 Zmpste24-/- MEFs 细胞衰老和细胞增殖的影响。结果表明，miR-342-5p 的过表达在一定程度上改善了细胞衰老表型，促进了 Zmpste24-/- MEFs 的细胞增殖并增加了 G2+M 细胞周期期。然而，在转染 miR-342-5p 抑制剂的野生型（WT）MEFs 中，很难观察到相反的细胞表型。生长停滞特异性基因 2（Growth-arrest-specific 2，GAS2）被鉴定为 Zmpste24-/- MEFs 中 miR-342-5p 的靶基因。此外，miR-342-5p 在 WT MEFs 复制性衰老过程中下调，而 Gas2 上调。综上所述，这些发现表明，下调的 miR-342-5p 通过抑制 GAS2 在体外参与调节 Zmpste24-/- MEFs 中的细胞增殖和细胞周期。
