Abstract
Myocardial infarction (MI) is a severe life-threatening disease caused by acute and persistent ischemia and hypoxia and eventually leads to heart failure and sudden death. Long noncoding RNAs (lncRNAs) play significant roles in the pathology, diagnosis, and development of various cardiovascular diseases, including MI. This study aimed to explore the effect and molecular mechanism of lncRNA miR-22 host gene (MIR22HG) on hypoxia-induced injury in AC16 cardiomyocytes. The expression of MIR22HG and miR-24 in hypoxia-treated AC16 cardiomyocytes was detected by quantitative real-time polymerase chain reaction. Cell viability, lactate dehydrogenase release, levels of aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB), and apoptosis were detected by Cell Counting Kit-8, lactate dehydrogenase (LDH) release assay, commercial enzyme-linked immune sorbent assay kits, and flow cytometry analysis, respectively. The protein levels of nuclear factor-kappa B (NF-κB) p65 and cytoplasmic inhibitor of kappa B alpha (IκBα) and phosphorylated IκBα were detected by western blot. Results showed that hypoxia treatment decreased viability and increased MIR22HG expression in AC16 cardiomyocytes. MIR22HG overexpression aggravated hypoxia-induced viability reduction, leakage of myocardial injury markers LDH, AST, and CK-MB, and apoptosis in AC16 cardiomyocytes, while MIR22HG knockdown elicited the reverse effects. MIR22HG overexpression enhanced NF-κB activation in hypoxia-treated AC16 cardiomyocytes. Inhibition of NF-κB pathway impaired the effects of MIR22HG overexpression on hypoxia-induced injury in AC16 cardiomyocytes. Moreover, MIR22HG knockdown inhibited the NF-κB pathway by upregulating miR-24 in AC16 cardiomyocytes. Inhibition of miR-24 resisted the effects of MIR22HG silencing on hypoxia-induced injury in AC16 cardiomyocytes. In conclusion, MIR22HG overexpression aggravated hypoxia-induced injury in AC16 cardiomyocytes via enhancing NF-κB activation by targeting miR-24.