title: ING1b-inducible microRNA203 inhibits cell proliferation.
abstract: BACKGROUND
  The ING family of type II tumour suppressors serve as both epigenetic 'readers' and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) 'writers' of the epigenetic histone code. The ING1 protein has also been implicated in regulating microRNA (miRNA) levels. In this study, we identify a link between ING1b and the miRNA epigenetic network.
  
  
  METHODS
  Primary fibroblasts infected with adenoviruses expressing GFP control or GFP plus ING1b were examined for alterations in miRNA profiles using a miRNA PCR array. Additional experiments confirmed specificity and consequences of altered miRNA expression.
  
  
  RESULTS
  MicroRNAs miR-203, miR-375, miR-449b and miR-200c were increased by ING1b overexpression. Ectopic expression of miR-203 inhibited U2OS and MDA-MB-231 cancer cell growth, and induced G1 cell cycle arrest in U2OS cells as estimated by flow cytometry. Transfection with miR-203 inhibitor reversed the proliferation inhibition induced by ING1b in U2OS cells. CHIP assays showed that ING1b bound to the promoter of miR-203. Western blot analyses showed that CDK6, c-Abl and Src were downregulated by the transfection of miR-203.
  
  
  CONCLUSIONS
  These results indicate that ING1b epigenetically regulates several miRNAs including miR-203. The several-fold increase in miR-203 by ING1b might inhibit cancer cell proliferation through coordinate downregulation of CDK6, c-Abl and Src.
authors: Department of Biochemistry and Molecular Biology, University of Calgary, Alberta T2N 4N1, Canada.
authors: J
authors: J
authors: Chen
authors: U M
authors: UM
authors: Tran
authors: U
authors: U
authors: Rajarajacholan
authors: S
authors: S
authors: Thalappilly
authors: K
authors: K
authors: Riabowol
mesh_terms: D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins