Background
Circular RNA (circRNA) has been shown to play an important role in a variety of cardiovascular diseases, including myocardial infarction (MI). However, the role of circRbms1 in MI progression remains unclear.
Conclusion
CircRbms1 regulated the miR-742-3p/FOXO1 axis to mediate hypoxia-induced cardiomyocyte injury, suggesting that circRbms1 might be an effective target for MI treatment.
Methods
An MI mouse model was constructed in vivo, and cardiomyocytes were cultured under hypoxia condition to induce a cardiomyocyte injury model in vitro. The expression levels of circRbms1, microRNA (miR)-742-3p, and forkhead box O1 (FOXO1) were determined by quantitative real-time PCR. Cell viability, migration, invasion, and apoptosis were measured using Cell Counting Kit-8 assay, transwell assay, and flow cytometry. Meanwhile, western blot analysis was used to examine the protein levels of apoptosis markers and FOXO1. Additionally, dual-luciferase reporter assay, RNA pull-down assay, and RIP assay were employed to verify the interactions between miR-742-3p and circRbms1 or FOXO1.
Results
CircRbms1 was upregulated in the heart tissues of MI mice and hypoxia-induced cardiomyocytes. Hypoxia induced cardiomyocyte injury by suppressing cell viability, migration, and invasion, and promoting apoptosis. Function experiments showed that circRbms1 overexpression aggravated hypoxia-induced cardiomyocyte injury, while its silencing relieved cardiomyocyte injury induced by hypoxia. Furthermore, circRbms1 sponged miR-742-3p. MiR-742-3p overexpression alleviated hypoxia-induced cardiomyocyte injury, and its inhibitor reversed the suppressive effect of circRbms1 silencing on hypoxia-induced cardiomyocyte injury. Further experiments showed that FOXO1 was a target of miR-742-3p, and its expression was positively regulated by circRbms1. The inhibitory effect of miR-742-3p on hypoxia-induced cardiomyocyte injury was reversed by FOXO1 overexpression.