microRNA-25 promotes cardiomyocytes proliferation and migration via targeting Bim.

microRNAs (miRNAs) are pleiotropic players in cardiac development. Recent evidence have suggested miRNAs as promisingly therapeutic targets for cardiac regeneration. This study aimed to reveal the potential effects of miR-25 on cardiomyocytes proliferation and migration. Sprague-Dawley rats received left coronary occlusion surgery to induce an in vivo model of myocardial ischemia/reperfusion (I/R) injury. Expression changes of miR-25 and Bim were tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot. Besides, primary neonatal and adult cardiomyocytes were transfected by the antisense oligonucleotides or mimic specific for miR-25, and then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), Boyden chamber, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay were respectively used to determine cardiomyocytes growth and migration. Binding effects of miR-25 on the 3'-untranslated region (3'-UTR) of Bim was assessed by dual-luciferase reporter assay. We found that miR-25 was low expressed, whereas Bim was highly expressed in I/R injury model and hypoxia-stimulated cardiomyocytes. Downregulation of miR-25 in neonatal and adult cardiomyocytes markedly reduced cell proliferation and migration, but promoted apoptosis. Consistently, downregulation of miR-25 decreased the expression of cyclin E2, cyclin D1, and CDK4, and increased the expression of p57 (KIP2) in cardiomyocytes. We additionally found that Bim was a target of miR-25. The inhibitory effects of miR-25 downregulation on cardiomyocytes survival and migration were all significantly attenuated when Bim was silenced. To sum up, our study demonstrates that miR-25 downregulation inhibits cardiomyocytes proliferation and migration, but promotes apoptosis. The role of miR-25 in cardiomyocytes was by targeting Bim.

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