Hsa_circ_0010729 regulates H2O2-induced myocardial injury by regulating miR-1184/RIPK1 axis

Abstract

BackgroundIschemia-reperfusion (I/R) is an important risk factor for cardiovascular diseases (CVDs) and cardiac transplantation, as I/R can cause myocardial cell hypoxia/reoxygenation (H/R) injury. Recent research has shown that circular RNAs (circRNAs) may affect the progress of H/R-induced myocardial injury, but the mechanism remains unknown. Our work explored the role of circ_0010729 in H2O2-induced myocardial injury. MethodsThe levels of circ_0010729, microRNA-1184 (miR-1184) and mRNA of receptor interacting serine/threonine kinase 1 (RIPK1) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in human cardiac myocytes (HCMs). Meanwhile, the protein level of RIPK1 was quantified by western blot analysis. Besides, the cell functions were examined by 5-Ethynyl-29-deoxyuridine (EdU) assay, flow cytometry assay, western blot and antioxidant indexes analysis. Furthermore, the interplay between miR-1184 and circ_0010729 or RIPK1 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of circ_0010729. ResultsThe levels of circ_0010729 RNA and RIPK1 protein were increased, and the miR-1184 was decreased in HCMs exposed to H2O2. In functional analysis, circ_0010729 deficiency restrained cell apoptosis and oxidative stress, whereas promoted cell proliferation in HCMs under H2O2 exposure. Moreover, miR-1184 inhibited the H2O2-induced myocardial injury by targeting RIPK1. Mechanistically, circ_0010729 acted as a miR-1184 sponge to regulate the level of RIPK1. ConclusionCirc_0010729 promotes H2O2-induced myocardial injury, and thus circ_001729 may be targeted as a potential therapy for H/R-induced myocardial injury.