title: MicroRNA-137 Negatively Regulates H₂O₂-Induced Cardiomyocyte Apoptosis Through CDC42.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland).
authors.forename: Junnan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland).
authors.forename: Rihao
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland).
authors.forename: Junduo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland).
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C581598:Cdc42 protein, mouse; C551799:MIRN137 microRNA, mouse; D035683:MicroRNAs; D006861:Hydrogen Peroxide; D020764:cdc42 GTP-Binding Protein