title: MicroRNA deregulation in right ventricular outflow tract myocardium in nonsyndromic tetralogy of fallot.
abstract: BACKGROUND
  Tetralogy of Fallot (TOF) is 1 of the most common heart defects in children, and the underlying mechanisms remain largely elusive. MicroRNAs (miRNAs) are a class of regulators of gene expression and are increasingly recognized for their roles in heart development.
  
  
  METHODS
  To identify miRNAs abnormally expressed in TOF, microarrays were used to analyze the miRNA expression profiles of 5 samples of myectomy tissues from right ventricular outflow tract (RVOT) obstruction of infants with nonsyndromic TOF and 3 age-matched normal RVOT tissues.
  
  
  RESULTS
  In total, 41 candidate miRNAs were identified. To further validate the microarray results, the 41 miRNAs were detected using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a larger independent population of tissue samples, including 21 from patients with TOF and 6 from normal controls; it was found that 18 miRNAs were expressed at significantly different levels. Bioinformatic analysis revealed that these miRNAs targeted a network of genes involved in heart development and human congenital heart diseases. Further in vitro studies indicated that upregulation of miR-424/424* promoted proliferation and inhibited migration of primary embryonic mouse cardiomyocytes, whereas miR-222 promoted cardiomyocyte proliferation and reduced the cardiomyogenic differentiation of P19 cells. The 3'UTR (3' untranslated region) luciferase assay revealed that miR-424/424* suppressed the expression of HAS2 and NF1, and their mRNAs were underexpressed in the RVOT myocardial tissues of TOF.
  
  
  CONCLUSIONS
  Eighteen miRNAs were identified as being deregulated in RVOT myocardial tissues from infants with nonsyndromic TOF, and in vitro experiments indicated that miR-424/424* and miR-222 are involved in cardiomyocyte proliferation and migration and the cardiomyogenic differentiation of P19 cells.
authors.affiliation: Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiao-Jiao
authors.initials: JJ
authors.lastname: Chang
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Ma
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Li
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Wang
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Huang
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D013771:Tetralogy of Fallot / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D046888:Tissue Array Analysis; D015854:Up-Regulation / Q000235:genetics; D014694:Ventricular Outflow Obstruction / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs