Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy

// Xixian Li 1 , Zhi Zeng 1 , Qingman Li 1 , Qiulin Xu 1 , Jiahe Xie 1 , Huixin Hao 1 , Guangjin Luo 1 , Wangjun Liao 2 , Jianping Bin 1 , Xiaobo Huang 1 , Yulin Liao 1 1 State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 2 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China Correspondence to: Xiaobo Huang, e-mail: chw47922@163.com Yulin Liao, e-mail: liao18@msn.com Keywords: Pathology Section, microRNA, cardiomyocytes, ischemia reperfusion, apoptosis, autophagy Received: May 28, 2015      Accepted: July 20, 2015      Published: July 29, 2015 ABSTRACT MiR-497 is predicted to target anti-apoptosis gene Bcl2 and autophagy gene microtubule-associated protein 1 light chain 3 B (LC3B), but the functional consequence of miR-497 in response to anoxia/reoxygenation (AR) or ischemia/reperfusion (IR) remains unknown. This study was designed to investigate the influences of miR-497 on myocardial AR or IR injury. We noted that miR-497 was enriched in cardiac tissues, while its expression was dynamically changed in murine hearts subjected to myocardial infarction and in neonatal rat cardiomyocytes (NRCs) subjected to AR. Forced expression of miR-497 (miR-497 mimic) induced apoptosis in NRCs as determined by Hoechst staining and TUNEL assay. In response to AR, silencing of miR-497 using a miR-497 sponge significantly reduced cell apoptosis and enhanced autophagic flux. Furthermore, the infarct size induced by IR in adenovirus (Ad)-miR-497 sponge infected mice was significantly smaller than in mice receiving Ad-vector or vehicle treatment, while Ad-miR-497 increased infarct size. The expression of Bcl-2 and LC3B-II in NRCs or in murine heart was significantly decreased by miR-497 mimic and enhanced by miR-497 sponge. These findings demonstrate that inhibition of miR-497 holds promise for limiting myocardial IR injury.