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MicroRNA-137 Negatively Regulates H2O2-Induced Cardiomyocyte Apoptosis Through CDC42

Junnan Wang, Rihao Xu, Junduo Wu, Zhibo Li

Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland)

Med Sci Monit 2015; 21:3498-3504

DOI: 10.12659/MSM.894648

Available online:

Published: 2015-11-13

BACKGROUND: Oxidative stress, inducing cardiomyocyte apoptosis or myocardial ischemia, is the major denominator of many cardiac diseases. In this study, we intended to explore the regulatory function of microRNA-137 (miR-137) in oxidative stress-induced cardiomyocyte apoptosis.
MATERIAL AND METHODS: Cardiomyocytes were extracted from newborn C57BL/6 mice and cultured in vitro. Apoptosis was induced by H2O2, and evaluated by TUNEL assay. The effect of cardiomyocyte apoptosis on gene expression of miR-137 was evaluated by qRT-PCR. Lentivirus was used to stably down-regulate miR-137, and the subsequent effects of miR-137 down-regulation on cardiomyocyte apoptosis, its targeted gene CDC42, and caspase pathway were evaluated by TUNEL assay, dual-luciferase reporter assay, and Western blot assay, respectively. Finally, CDC42 was down-regulated by siRNA and its effect on miR-137-mediated cardiomyocyte apoptosis protection was examined.
RESULTS: H2O2 induced significant apoptosis and up-regulated miR-137 in cardiomyocytes, whereas lentivirus-mediated miR-137 down-regulation protected against apoptosis. CDC42 was the direct target gene of miR-137 and proteins of CDC42, caspase-3, and caspase-9 were all regulated by miR-137 down-regulation in cardiomyocyte apoptosis. SiRNA-mediated CDC42 down-regulation reversed the protection of miR-137 down-regulation against cardiomyocyte apoptosis.
CONCLUSIONS: Our work demonstrated miR-137 and CDC42 are critical regulators in cardiomyocyte apoptosis. It may help to identify the molecular targets to prevent myocardial injury in human patients.

Keywords: Apoptosis - genetics, Animals, Cells, Cultured, Hydrogen Peroxide - pharmacology, Mice, Mice, Inbred C57BL, MicroRNAs - metabolism, Myocardial Ischemia - pathology, Myocytes, Cardiac - metabolism, Oxidative Stress - drug effects, Up-Regulation - drug effects, cdc42 GTP-Binding Protein - metabolism