title: MicroRNA-92a inhibition attenuates hypoxia/reoxygenation-induced myocardiocyte apoptosis by targeting Smad7.
abstract: BACKGROUND
  MicroRNAs (miRNAs) regulate a lot of physiological and pathological processes, including myocardial ischemia/reperfusion. Recent studies reported that knockdown of miR-92a could attenuate ischemia/reperfusion-induced myocardial injury. In the present study, we examined the potential anti-apoptotic effects of miR-92a in a rat myocardiocyte cell line, and the possible role of Smad7 in such actions.
  
  
  RESULTS
  In a preliminary bioinformatic analysis, we identified SMAD family member 7 (Smad7) as a potential target for miR-92a. A luciferase reporter assay indeed demonstrated that miR-92a could inhibit Smad7 expression. Myocardial ischemia/reperfusion was simulated in rat H9c2 cells with 24-h hypoxia followed by 12-h reoxygenation. Prior to hypoxia/reoxygenation, cells were transfected by miR-92a inhibitor. In some experiments, cells were co-transfected with siRNA-Smad7. The miR-92a inhibitor dramatically reduced the release of lactate dehydrogenase and malonaldehyde, and attenuated cardiomyocyte apoptosis. The miR-92a inhibitor increased SMAD7 protein level and decreased nuclear NF-κB p65 protein. Effects of the miR-92a inhibitor were attenuated by co-transfection with siRNA-Smad7.
  
  
  CONCLUSIONS
  Inhibiting miR-92a can attenuate myocardiocyte apoptosis induced by hypoxia/reoxygenation by targeting Smad7.
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Busheng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Canbo
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Anqing
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D005786:Gene Expression Regulation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D018716:Molecular Mimicry; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009841:Oligonucleotides / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051906:Smad7 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000592377:MIRN92 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C498145:Rela protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D051996:Transcription Factor RelA; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D010100:Oxygen