Circular RNA ANKIB1 alleviates hypoxia-induced cardiomyocyte injury by modulating miR-452-5p/SLC7A11 axis.

Abstract

Acute myocardial infarction (AMI) is a common cardiovascular disease worldwide. Circular RNAs (circRNAs) have been shown to exert essential roles in the progression of AMI. However, it remains unclear whether circANKIB1 protects cardiomyocytes from hypoxia-induced injury. The aim of the study was to elucidate the function and mechanisms of circANKIB1 in AMI. The expression of RNA was estimated using a quantitative real-time polymerase chain reaction (qPCR) assay, and the level of protein was determined with the use of western blot analysis. Methyl thiazolyl tetrazolium (MTT) assay was introduced to test cell viability, and a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to detect apoptosis. The relative levels of ferrous ion (Fe2+), reactive oxygen species (ROS) and malondialdehyde (MDA) were measured with their corresponding detection kits. The potential target of circANKIB1 and miR-452-5p was predicted using the StarBase database and verified by employing a dual luciferase reporter assay. This study showed a significant decrease in circANKIB1 in hypoxia-treated H9c2 cells. Hypoxic exposure significantly reduced the viability of H9c2 cells and the expression of GPX4, and increased the content of Fe2+, ROS and MDA. These effects were reversed by the overexpression of circANKIB1. Additionally, miR-452-5p was found to be a direct target of circANKIB1, and the miR-452-5p mimic significantly eliminated the protective effect of circANKIB1 overexpression in hypoxia-induced cells. In addition, miR-452-5p could bind to SLC7A11 and negatively regulate its expression. The knockdown of SLC7A11 abolished the effect of circANKIB1 overexpression on hypoxia-induced cardiomyocyte injury. This investigation revealed for the first time that circANKIB1 regulated signaling of the miR-452-5p/SLC7A11 axis, thereby ameliorating hypoxia-induced cardiomyocyte injury. These findings suggest that circANKIB1 might be a useful adjunct in the treatment of AMI.