lncRNA Oip5‐as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR‐29a to activate the SIRT1/AMPK/PGC1α pathway

作者：Xiaowei Niu, Shuangshuang Pu, Chun Ling, Jizhe Xu, Jing Wang, Shaobo Sun, Yali Yao, Zheng Zhang · 发表于：Cell Proliferation · 年份：2020 · DOI：10.1111/cpr.12818 · 被引用次数：106 · 研究领域：Cancer-related molecular mechanisms research、Cardiac Ischemia and Reperfusion、Metabolism, Diabetes, and Cancer

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 ...