title: Up-regulation of miR-182 by β-catenin in breast cancer increases tumorigenicity and invasiveness by targeting the matrix metalloproteinase inhibitor RECK.
abstract: BACKGROUND
  MiR-182 is a member of the miR-183 cluster located at human chromosome 7q32 region and is up-regulated in human cancers. We study the regulation of miR-182 expression and its oncogenic role.
  
  
  METHODS
  MiR-182 level was investigated by real-time reverse transcription-PCR. Chromatin immunoprecipitation assay was used to confirm promoter binding of transcription factors. The correlation between miR-182 and RECK was analyzed by Western blotting, real-time RT-PCR and 3(')-untranslated region reporter assay. Zymography, matrix metalloproteinase activity, invasion and colony formation were used to study the tumorigenic activity.
  
  
  RESULTS
  MiR-182 is over-expressed in human breast tumor tissues and cell lines. Inhibition or knockdown of β-catenin reduced miR-182 level in MDA-MB-231 cells. ChIP assay confirmed the binding of β-catenin on miR-182 promoter. Anti-miR-182 increased the MMP inhibitor RECK protein in MDA-MB-231 cells while pre-miR-182 reduced RECK protein but not mRNA in normal mammary epithelial H184B5F5/M10 cells. Restoration of RECK protein by anti-miR-182 attenuated MMP-9 activity, cell invasion and colony formation. Ectopic expression of miR-182 inhibited restoration of RECK protein by β-catenin inhibitor indicating miR-182 is important for β-catenin-induced down-regulation of RECK. An inverse association between miR-182 and RECK was demonstrated in breast tumor tissues.
  
  
  CONCLUSIONS
  We provide evidence that miR-182 is up-regulated by β-catenin signaling pathway in breast cancer and its up-regulation increases tumorigenicity and invasiveness by repressing RECK.
  
  
  CONCLUSIONS
  Our data demonstrate for the first time that miR-182 expression is controlled by β-catenin. In addition, we identify a new miR-182 target RECK which is important for miR-182-induced tumorigenesis.
authors: Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
authors: Chi-Hsiang
authors: CH
authors: Chiang
authors: Ming-Feng
authors: MF
authors: Hou
authors: Wen-Chun
authors: WC
authors: Hung
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D015854:Up-Regulation; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C495270:CTNNB1 protein, human; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C115460:RECK protein, human; D051176:beta Catenin