MiR-96 promotes myocardial infarction-induced apoptosis by targeting XIAP

Regulatory network of miR-96 in AMI. MiR-96 promotes cardiomyocyte apoptosis and myocardial dysfunction in AMI progression through directly targeting XIAP to upregulate Cleaved caspase-3, Bax and downregulate Bcl-2. [Display omitted] •MiR-96 was significantly upregulated in the ischemic heart of AMI mice.•MiR-96 inhibitor reduced cell apoptosis of cardiomyocytes (CMs) in response to H2O2.•MiR-96 promoted AMI progression by directly targeting XIAP. Acute myocardial infarction (AMI) has becoming a common leading cause of sudden death worldwide. MiR-96 has been identified that can target anti-apoptotic related genes in various human diseases. However, its role in AMI remains unclear. In this study, we found that miR-96 was significantly upregulated in the ischemic heart of MI mice (mice with myocardial infarction) and also in the H2O2-treated neonatal rat ventricular cardiomyocytes (CMs). In response H2O2, miR-96 inhibitor could significantly promote cell viability and reduce cell apoptosis of CMs, and inhibit the expression of Cleaved caspase-3 and Bax, while promote Bcl-2 expression. In addition, downregulation of miR-96 remarkedly reduced the infarct size and the percentages of apoptotic cells in the heart tissues of MI mice, and then protected against the damaged cardiac function. Moreover, we identified that XIAP (X-linked inhibitor of apoptosis) acted as a direct target gene of miR-96, meanwhile si-XIAP could obviously reverse miR-96 inhibitor induced protective effect in H2O2-treated CMs Taken together, our study demonstrated that miR-96 promoted AMI progression by directly targeting XIAP, and inhibiting the anti-apoptotic function of XIAP (Graphical abstract), which provided a novel therapeutic target for AMI treatment.