文献类型：期刊文献

英文题名：lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway

作者：Niu, Xiaowei[1,2,3,4];Pu, Shuangshuang[5];Ling, Chun[6];Xu, Jizhe[1,2,3,4];Wang, Jing[7];Sun, Shaobo[8];Yao, Yali[1,2,3,4];Zhang, Zheng[1,2,3,4]

第一作者：Niu, Xiaowei

通信作者：Zhang, Z[1]

机构：[1]Lanzhou Univ, Hosp 1, Heart Ctr, 1 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China;[2]Lanzhou Univ, Hosp 1, Gansu Clin Med Res Ctr Cardiovasc Dis, Lanzhou, Gansu, Peoples R China;[3]Lanzhou Univ, Hosp 1, Gansu Key Lab Cardiovasc Dis, Lanzhou, Gansu, Peoples R China;[4]Lanzhou Univ, Hosp 1, Qual Improvement Project Diag & Treatment Complic, Lanzhou, Gansu, Peoples R China;[5]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[6]First Peoples Hosp Chuzhou, Chuzhou, Anhui, Peoples R China;[7]Lanzhou Univ, Hosp 1, Dept Gerontol, Lanzhou, Gansu, Peoples R China;[8]Gansu Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Hosp 1, Heart Ctr, 1 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 1, Heart Ctr, 1 Donggang West Rd, Lanzhou 730000, Gansu, Peoples R China.

年份：2020

卷号：53

期号：6

外文期刊名：CELL PROLIFERATION

收录：;Scopus(收录号：2-s2.0-85085602303);WOS:【SCI-EXPANDED(收录号:WOS:000535898600001)】；

基金：The authors acknowledge financial support from Research Project of Gansu Provincial Administration of Traditional Chinese Medicine (GZK-2018-48) and the Foundation for Scientific Research of the First Hospital of Lanzhou University.

语种：英文

外文关键词：apoptosis; microRNA-29a; mitochondria; myocardial ischaemia; reperfusion injury; Opa-interacting protein 5-antisense transcript 1; sirtuin 1

摘要：Objectives Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non-coding RNA (lncRNA) Oip5-as1 in regulating mitochondria-mediated apoptosis during MI/R injury. Materials and methods Sprague-Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT-qPCR and Western blot were used to evaluate gene and protein levels. CCK-8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5-as1. The dual-luciferase gene reporter assay and RIP assay were conducted as needed. Results Oip5-as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5-as1 overexpression alleviated reactive oxygen species-driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5-as1 acted as a competing endogenous RNA of miR-29a and thus decreased its expression. Inhibition of miR-29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR-29a reversed the anti-apoptotic effect of Oip5-as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR-29a. Oip5-as1 upregulated SIRT1 expression and activated the AMPK/PGC1 alpha pathway by targeting miR-29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527. Conclusions Oip5-as1 suppresses miR-29a leading to activation of the SIRT1/AMPK/PGC1 alpha pathway, which attenuates mitochondria-mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.