Drug Design, Development and Therapy (Feb 2020)
miR-346 Inhibited Apoptosis Against Myocardial Ischemia-Reperfusion Injury via Targeting Bax in Rats
Abstract
Xiangwei Lv,1,* Pan Lu,1,* Yisen Hu,2 Tongtong Xu1 1Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tongtong XuDepartment of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86 773-2807731Email [email protected]: Myocardial ischemia-reperfusion injury (MIRI) is a common pathophysiological process after occlusion of the blood vessels to restore blood supply. Apoptosis is one of the ways of myocardial cell death in this process. MicroRNAs (miRNAs), a class of short and noncoding RNAs, are involved in multiple biological processes by post-transcriptionally targeting their downstream effectors. To date, whether miRNAs exert biological effects in myocardial ischemia-reperfusion (I/R) injury remains to be further studied.Methods: In this study, we induced MIRI model by ligating rat left anterior descending artery (LAD) for 30 mins and reperfusion for 2 hrs. The differential expression profile of miRNAs in rat models of MIRI was analyzed by miRNAs sequencing.Results: We found that miRNAs sequencing analysis showed the expressions of 15 types of miRNAs, including miR-346, were downregulated and 29 types of miRNAs were elevated in the MIRI rat model. We observed the key regulator of apoptosis Bax was a predicted downstream target of miR-346 using online software TargetScan. And luciferase reporter assay was utilized to certify this prediction. Over-expression of miR-346 can attenuate myocardial injury and narrow infarct area by inhibiting myocardial cell apoptosis in rat models.Conclusion: This study revealed a novel pathway, miR-346/Bax axis, in the regulation of apoptosis in MIRI and which might be a new molecular mechanism and therapeutic target.Keywords: miR-346, myocardial ischemia-reperfusion injury, apoptosis, Bax