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.
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The analysed data sets generated during the study are available from the corresponding author on reasonable request.
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This work was supported by the Self-financing project of Hebei Science and Technology Plan [182777148].
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Substantial contributions to conception and design: ZW. Data acquisition, data analysis and interpretation: DS, NZ, TY, HT. Drafting the article or critically revising it for important intellectual content: ZW. Final approval of the version to be published: All authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: All authors.
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Wang, Z., Shi, D., Zhang, N. et al. MiR-217 promotes endothelial cell senescence through the SIRT1/p53 signaling pathway. J Mol Histol 52, 257–267 (2021). https://doi.org/10.1007/s10735-020-09945-x
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DOI: https://doi.org/10.1007/s10735-020-09945-x