Knockdown of circ_0001379 attenuates hypoxia/reoxygenation-induced cardiomyocyte apoptosis and inflammatory response by mir-98-5p/sox6 axis

Background: Aberrant expression of circular RNAs (circRNAs) has been revealed to have crucial roles in the pathological processes of cardiovascular disease. Here, this study aimed to investigate the role and mechanism of circ_0001379 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury to explore the potential action of circ_0001379 in acute myocardial infarction (AMI). Methods: Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and western blot. Cell counting kit-8 assay, 5-ethynyl-2 '-deoxyuridine assay, and flow cytometry were used to detect cardiomyocyte proliferation and apoptosis, respectively. The activity of IL-1 beta, IL-6, and TNF-alpha was determined by ELISA analysis. The target relationship between miR-98-5p and circ_0001379 or SOX6 (SRY-Box Transcription Factor 6) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0001379 was highly expressed in AMI mouse model and H/R-induced cardiomyocytes. Functionally, circ_0001379 silencing attenuated H/R-evoked cardiomyocyte apoptosis and inflammatory response. Mechanistically, circ_0001379 functioned as a sponge for miR-98-5p, which directly targeted SOX6. Moreover, circ_0001379 could regulate SOX6 expression via sponging miR-98-5p. Further rescue experiments showed that inhibition of miR-98-5p reversed the protective effects of circ_0001379 silencing on H/R-induced cardiomyocytes. Besides that, miR-98-5p overexpression abolished H/R-evoked cardiomyocyte apoptosis and inflammatory response, while this condition was abated by SOX6. Conclusion: Circ_0001379 silencing protects cardiomyocytes from H/R-induced apoptosis and inflammatory response by miR-98-5p/SOX6 axis, suggesting a novel therapeutic strategy for AMI prevention.