1. lncRNA MIRF Promotes Cardiac Apoptosis through the miR-26a-Bak1 Axis
- Author
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Xiaomin Su, Lifang Lv, Yue Li, Ruonan Fang, Rui Yang, Chao Li, Tianyu Li, Di Zhu, Xuelian Li, Yuhong Zhou, Hongli Shan, and Haihai Liang
- Subjects
myocardial infarction ,apoptosis ,lncRNA MIRF ,miR-26a ,Bak1 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Acute myocardial infarction (AMI) is the leading cause of death worldwide. Identifying the pathways that block cardiac cell death is a therapeutic strategy for ischemic heart disease. We found that long noncoding RNA (lncRNA) myocardial infarction-regulatory factor (MIRF) promoted ischemic myocardial injury by regulating autophagy through targeting miR-26a. However, the role of MIRF-miR-26a in apoptosis during AMI has not been delineated. In this study, we found the downregulation of miR-26a both in the heart of myocardial infarction (MI) mice and in H2O2-treated cardiomyocytes. miR-26a silencing resulted in apoptosis, whereas overexpression of miR-26a attenuated H2O2-induced apoptosis through promoting mitochondrial ATP content and increasing mitochondrial membrane potential (MMP). Moreover, forced expression of miR-26a protected against MI-induced cardiac injury and attenuated cardiac apoptosis. Further studies showed that miR-26a inhibited apoptosis through regulation of Bak1. Furthermore, MIRF decreased ATP content and MMP through regulating miR-26a, which then promoted the cardiomyocyte apoptosis. In contrast, deficiency of MIRF promoted mitochondrial ATP content and increased MMP, and then inhibited MI or H2O2-induced cardiac apoptosis, which was abolished by miR-26a inhibitor. Taken together, these results suggested that MIRF contributed to cardiomyocyte apoptosis through modulating Bak1 by regulation of miR-26a, which can be a potential therapeutic target for the treatment of ischemic heart disease.
- Published
- 2020
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