title: Combinatorial microRNAs suppress hypoxia-induced cardiomyocytes apoptosis.
abstract: OBJECTIVE
  Our previous in silico analysis revealed potential synergy in the activities of micro(mi)RNAs in myocardial infarction. The present study investigated whether miR-1 and -21 act synergistically to protect against cardiomyocytes apoptosis.
  
  
  METHODS
  Cell survival was analyzed with cell viability assay; apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling, and the caspase-3 activity assay; and protein expression level was determined by western blotting.
  
  
  RESULTS
  MiR-1:miR-21 and several other miRNA pairs were evaluated for their potentially synergistic effects against myocardial hypoxia in neonatal rat ventricular cardiomyocytes. Lower combination indices suggested that miRNA pairs acted synergistically to inhibit apoptosis; miR-1 and -21 jointly blocked hypoxia-induced cardiomyocytes apoptosis. Moreover, combined application of miR-1 and -21 activated Akt and blocked hypoxia-induced upregulation of p53 in these cells.
  
  
  CONCLUSIONS
  MiR-1 and -21 exert synergistic effects against hypoxia-induced cardiomyocytes apoptosis. These results provide a basis for the development of combined miRNA-based therapeutics to treat cardiovascular diseases.
authors.affiliation: Institute of Clinical Pharmacology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Xu
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.forename: Huibin
authors.initials: H
authors.lastname: Liu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C546082:mirn21 microRNA, rat; D051057:Proto-Oncogene Proteins c-akt