MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis.

M-Y Sun, L-P Li

European review for medical and pharmacological sciences 2020 Jun

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Recovery of blood flow after ischemic cardiomyopathy can lead to aggravation of myocardial injury. This is very detrimental to the patient's prognosis. The purpose of this study was to investigate the effects and mechanisms of microRNA-140-5p (miR-140-5p) on myocardial ischemia-reperfusion injury (IRI). We made the myocardial IRI model in rats and detected the expression of miR-140-5p. Anta-miR-140-5p was administered intravenously in the tail of rats. Then, we used 2, 3, 5-triphenyl tetrazolium chloride staining, cardiac function test, and histological experiment to observe the changes in myocardial infarct size, cardiac function, and cardiomyocyte apoptosis in rats. In in vitro experiments, we induced the damage of H9c2 cells by hypoxia/reoxygenation (H/R) model and detected the effects of miR-140-5p on the proliferation ability and apoptosis level of H9c2 cells. TargetScan database was used to predict the binding target of miR-140-5p and we verified the effect of miR-140-5p on the target through Dual-Luciferase reporter assay. MiR-140-5p is highly expressed in myocardial tissue of IRI rats and anta-miR-140-5p can reduce myocardial infarct area, improve cardiac function, and reduce the rate of myocardial cells apoptosis in rats. The expression of miR-140-5p in H/R-induced H9c2 cells was higher than that in the control group. MiR-140-5p inhibitor was found to promote the proliferation and decrease the apoptosis level of H9c2 cells, while miR-140-5p mimic was the opposite. The TargetScan system predicts the presence of binding sites for miR-140-5p and B-cell lymphoma-2 like 1 (BCL2L1). The Dual-Luciferase reporter assay found that miR-140-5p can bind to BCL2L1 and promote its degradation. In addition, the inhibition of BCL2L1 was found to promote apoptosis in H9c2 cells. In myocardial IRI, miR-140-5p targets BCL2L1 and promotes its degradation, thereby inducing myocardial apoptosis.

Citation

M-Y Sun, L-P Li. MiR-140-5p targets BCL2L1 to promote cardiomyocyte apoptosis. European review for medical and pharmacological sciences. 2020 Jun;24(11):6311-6322