Circular RNA MGAT1 regulates cell proliferation and apoptosis in hypoxia-induced cardiomyocytes through miR-34a/YAP1 axis

Congenital heart disease (CHD) has severe morbidity and mortality worldwide. Evidence suggests that circularRNAs (circRNAs) are involved in the pathogenesis of human CHD. However, the regulatory mechanism remains uncertain. This study aimed to explore that mechanism. The levels of circular RNA MGAT1 (circMGAT1) and miR-34a were measured by quantitative polymerase chain reaction (qRT-PCR). Expression of yes-associated protein isoform 1 (YAP1) was assessed by western blot. Caspase-3 activity was evaluated by Caspase 3 Activity Assay Kit. CCK-8 assay was carried out to detect cell proliferation of hypoxia-induced AC16 cells. Cell Apoptosis was analyzed by flow cytometry. In addition, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-34a and circMGAT1 or YAP1 in vitro. The level of circMGAT1 was downregulated, while miR-34a was strikingly increased in CHD tissues and hypoxia-induced AC16 cells. CircMGAT1 was a Sponge of miR-34a, and circMGAT1 targeted miR-34a to regulate cell proliferation and Apoptosis in hypoxia-induced cardiomyocytes. Dual-luciferase reporter and RIP-assay verified that miR-34a directly targeted YAP1, and the expression of YAP1 was significantly suppressed by miR-34a mimics but was enhanced by miR-34a inhibitor. Interestingly, YAP1 restored the effect of miR-34a on cell proliferation and Apoptosis in hypoxia-induced AC16 cells. Besides, circMGAT1 sponged miR-34a to regulate the expression of YAP1. In conclusion, circMGAT1 inhibited cell Apoptosis and enhanced cell proliferation by regulating the miR-34a/YAP1 axis, providing a therapy target for the treatment of human CHD.