MiR-217 promotes endothelial cell senescence through the SIRT1/p53 signaling pathway.

Abstract

Studies have shown that miR-217 can induce cell senescence, but its mechanism of action in vascular endothelial cell senescence is less reported. Therefore, this study aimed to investigate how miR-217 plays a role in endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) were used to replicate the aging model, and the population doubling levels (PDLs) during cell passage were counted. Senescence-associated β-galactosidase (SA-β-gal) staining, Real-time quantitative PCR (RT-qPCR), MTT assay, Transwell, and tube formation were used to detect the effects of miR-217 on young and senescent HUVECs. Targetscan7.2 and luciferase assay predicted and verified the relationship between miR-217 and the target gene, and the expression of silent information regulator 1 (SIRT1) and p53 was detected by RT-qPCR and western blot. In addition, SA-β-gal staining detected the effects of miR-217 inhibitor and SIRT1 on senescent HUVECs. MiR-217 was upregulated in senescent endothelial cells. Overexpression of miR-217 promoted the increase of SA-β-gal positive cells, and inhibited proliferation, migration and angiogenesis during endothelial cell growth. Furthermore, SIRT1 was a target gene of miR-217. Simultaneous silencing of SIRT1 reversed the effect of miR-217 inhibitor on the reduction of SA-β-gal positive-staining cells. Our data suggest that overexpression of miR-217 promoted vascular endothelial cell senescence by targeting the SIRT1/p53 signaling pathway, which may provide a new basis for studying the mechanism of action in vascular endothelial cell senescence.