RESUMEN
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 metalloproteinasedeficient mice, a progeria mouse model of HutchinsonGilford Progeria Syndrome. Previous studies have shown that miR3425p, an intronic microRNA (miRNA/miR) reportedly involved in ageing associated diseases, is downregulated in Zmpste24/ MEFs. However, whether miR3425p is associated with the premature senescence phenotype of Zmpste24/ MEFs remains unclear. Thus, the present study investigated the effects of miR3425p on cellular senescence and cell proliferation in Zmpste24/ MEFs. The results showed that miR3425p 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 wildtype (WT) MEFs transfected with the miR3425p inhibitor. Growtharrestspecific 2 (GAS2) was identified as a target gene of miR3425p in Zmpste24/ MEFs. In addition, miR3425p was identified to be downregulated in WT MEFs during replicative senescence, while Gas2 was upregulated. Taken together, these findings suggest that downregulated miR3425p is involved in regulating cell proliferation and cell cycles in Zmpste24/ MEFs by suppressing GAS2 in vitro.