MicroRNA-17-5p mediates hypoxia-induced autophagy and inhibits apoptosis by targeting signal transducer and activator of transcription 3 in vascular smooth muscle cells

MicroRNA-17-5p 通过靶向血管平滑肌细胞中的信号转导和转录激活因子 3 介导缺氧诱导的自噬并抑制细胞凋亡

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作者:Ming-Xiu Hao, Xing Wang, Kun-Li Jiao

Abstract

The aim of the present study was to investigate hypoxia-induced apoptosis and autophagy in vascular smooth muscle cells (VSMCs) and the underlying molecular mechanisms of microRNA (miR)-17-5p responses in an anaerobic environment. The results revealed that miR-17-5p expression was significantly upregulated in VSMCs subjected to hypoxic conditions (P<0.05) and lower miR-17-5p levels were observed in ethyl 3,4-dihydroxybenzoate-treated and hypoxia inducible factor-1 loss-of-function cells. Additionally, it was demonstrated that miR-17-5p is associated with hypoxia-induced autophagy, which was confirmed by upregulating the light chain 3-II/LC3-I ratio and downregulating nucleoporin p62. Cell apoptosis was inhibited in response to hypoxia, and levels of pro-apoptotic proteins B-cell lymphoma 2-associated X protein and p-caspase were markedly decreased when VSMCs were subjected to hypoxic conditions. Furthermore, expression of signal transducer and activator of transcription 3 (STAT3) decreased when cells were transfected with overexpressing miR-17-5p and subjected to hypoxic conditions, and the combination of miR-17-5p loss-of-function and hypoxia induced greater upregulation in the protein expression of STAT3 compared with a single treatment for hypoxia in VSMCs. In conclusion, miR-17-5p may be a novel hypoxia-responsive miR and hypoxia may induce protective autophagy and anti-apoptosis in VSMCs by targeting STAT3.

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