Circ_0001206 regulates miR‐665/CRKL axis to alleviate hypoxia/reoxygenation‐induced cardiomyocyte injury in myocardial infarction

Abstract

Aims Myocardial infarction (MI) is a type of cardiovascular disease caused by myocardial necrosis. Growing evidences have suggested that circular RNAs (circRNAs) play crucial roles in cardiac hypoxia/reoxygenation (H/R)-induced injury of MI. Methods and resultsHypoxia/reoxygenation model of H9C2 cells was established and circ_0001206 expression was detected via quantitative real-time polymerase chain reaction. Ribonuclease R (RNase R) and Actinomycin D (Act D) assays verified the stability. Cell counting kit-8 (CCK-8), western blot, TUNEL, and flow cytometry assays evaluated cell viability and cell apoptosis. RNA pull-down, RNA binding protein immunoprecipitation (RIP), and luciferase reporter assays explored the mechanisms underlying MI. All experimental data were presented with mean ± standard deviation (SD) and P < 0.05 indicated statistical significance. Circ_0001206 was low-expressed in H9C2 cells under H/R treatment. Circ_0001206 was formed by cyclization of CRK like proto-oncogene, adaptor protein (CRKL). Circ_0001206 overexpression promoted cell viability and inhibited cardiomyocyte apoptosis. It was confirmed that circ_0001206 regulated CRKL expression via acting as a competing endogenous RNA (ceRNA) of microRNA-665 (miR-665). CRKL played a protective role in MI. Conclusions Circ_0001206 regulates miR-665/CRKL axis to alleviate H/R-induced cardiomyocyte injury in MI. Our findings suggest that circ_0001206 might be a potential target for MI treatment.

The circRNA-miRNA/RBP regulatory network in myocardial infarction

“…In H/R-treated CMs, circ_0001206 overexpression enhanced cell viability and suppressed apoptosis. The results suggested the cardioprotective role of circ_0001206 ( Wang et al, 2022 ). Circ_0001206 could bind to miR-665, which was validated to target CRKL.…”

“…CRK like proto-oncogene, adaptor protein (CRKL) has been found to mitigate CM injury induced by hypoxia/reoxygenation (H/R) in MI ( Zhang et al, 2015 ). In this study, H/R treatment was used to construct an in vitro MI model ( Wang et al, 2022 ). Wang et al found a circRNA produced by the CRKL gene, circ_0001206 ( Wang et al (2022) .…”

“…In this study, H/R treatment was used to construct an in vitro MI model ( Wang et al, 2022 ). Wang et al found a circRNA produced by the CRKL gene, circ_0001206 ( Wang et al (2022) . Circ_0001206 was significantly downregulated in H/R-treated CMs and the MI mouse model.…”

“…Moreover, miR-665 overexpression inhibited the protective effect of circ_0001206. Taken together, circ_0001206 attenuated H/R-induced CM injury by modulating the miR-665-CRKL axis ( Wang et al, 2022 ).…”

Circular RNAs: Biogenesis, Biological Functions, and Roles in Myocardial Infarction

“…Circular RNAs are distributed extensively throughout the cardiovascular system and vary dramatically in their expression levels in the context of different cardiac disorders, such as acute MI, angina pectoris, and myocarditis, and function as regulators of heart development, cardiac function, and stress response. Plenty of research has indicated that the critical features of circular RNAs are related to MI [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. These circRNAs with altered levels have been found to regulate cardiac cell death after the onset of MI, such as apoptosis, autophagy, necrosis, and inflammatory infiltration, and also regulate myocardial collagen deposition and fibrosis during the healing stage of MI.…”