miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP
miR-146a-5p Mediates Intermittent Hypoxia-Induced Injury in H9c2 Cells by Targeting XIAP
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miR-146a-5p 通过靶向 XIAP 介导 H9c2 细胞间歇性缺氧诱导的损伤
DOI：
10.1155/2019/6581217
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Lin, Qichang
中科院分区：
文献类型：
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作者：
Lin, Guofu;Huang, Jiefeng;Lin, Qichang
microRNAs（miRNAs）已成为心血管疾病病理生理过程中的关键调节因子。然而，其在阻塞性睡眠呼吸暂停（OSA）引起的心脏损伤中的作用尚不清楚。本研究旨在探讨miR-146 a-5 p在间歇性缺氧（IH）诱导的心肌损伤中的作用及其可能的分子机制。将H9 c2细胞暴露于IH条件下，RT-qPCR检测miR-146 a-5 p的表达水平。分别通过细胞计数试剂盒-8（CCK-8）、流式细胞术和蛋白质印迹法评估细胞活力、细胞凋亡和凋亡相关蛋白的表达。通过双荧光素酶报告基因分析确定miR-146 a-5 p的靶基因。IH显著降低细胞活力，但促进细胞凋亡。同时，IH后H9 c2细胞中miR-146 a-5 p表达水平增加。随后的实验表明，IH诱导的损伤通过miR-146 a-5 p沉默而减轻。通过生物信息学分析预测了X连锁凋亡抑制蛋白（XIAP），并进一步证实其为miR-146 a-5 p的直接靶基因。令人惊讶的是，IH下miR-146 a-5 p抑制的效果可以通过下调XIAP表达来逆转。结论：miR-146 a-5 p可通过靶向XIAP抑制H9 c2细胞的存活，促进其凋亡，从而加重IH诱导的H9 c2细胞损伤，为进一步研究OSA相关心脏损伤机制奠定基础。
MicroRNAs (miRNAs) have emerged as key modulators in the pathophysiologic processes of cardiovascular diseases. However, its function in cardiac injury induced by obstructive sleep apnea (OSA) remains unknown. The aim of the current study was to identify the effect and potential molecular mechanism of miR-146a-5p in intermittent hypoxia(IH)- induced myocardial damage. We exposed H9c2 cells to IH condition; the expression levels of miR-146a-5p were detected by RT-qPCR. Cell viability, cell apoptosis, and the expressions of apoptosis-associated proteins were assessed via Cell Counting Kit-8 (CCK-8), flow cytometry, and western blotting, respectively. Target genes of miR-146a-5p were confirmed by dual-luciferase reporter assay. IH remarkably lowered viability but enhanced cell apoptosis. Concomitantly, the miR-146a-5p expression level was increased in H9c2 cells after IH. Subsequent experiments showed that IH-induced injury was alleviated through miR-146a-5p silence. X-linked inhibitor of apoptosis protein (XIAP) was predicted by bioinformatics analysis and further confirmed as a direct target gene of miR-146a-5p. Surprisingly, the effect of miR-146a-5p inhibition under IH may be reversed by downregulating XIAP expression. In conclusion, our results demonstrated that miR-146a-5p could attenuate viability and promote the apoptosis of H9c2 by targeting XIAP, thus aggravating the H9c2 cell injury induced by IH, which could enhance our understanding of the mechanisms for OSA-associated cardiac injury.