Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let-7a-5p/IGF2BP3 in cardiomyocytes

Abstract

Circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let-7a-5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time-dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R-mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let-7a-5p, subsequently regulating insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)-dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA-101237/let-7a-5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.