title: microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer.
abstract: BACKGROUND
  The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers.
  
  
  METHODS
  Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To investigate the function of miR-183, we used a miR-183 knockdown inhibitor in cell growth and wound-healing assays. We used several algorithms and confirmed that they are directly regulated by miR-183.
  
  
  RESULTS
  We identified three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues compared with that in matched normal prostate tissues. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher pT and shorter overall survival. MiR-183 knockdown decreased cell growth and motility in PC cells and significantly decreased prostate tumour growth in in vivo nude mice experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183.
  
  
  CONCLUSIONS
  Our data suggest that oncogenic miR-183 may be useful as a new PC biomarker and that inhibition of miR-183 expression may be therapeutically beneficial as a PC treatment.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ueno
authors.forename: H
authors.initials: H
authors.lastname: Hirata
authors.forename: V
authors.initials: V
authors.lastname: Shahryari
authors.forename: G
authors.initials: G
authors.lastname: Deng
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Z L
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Y
authors.initials: Y
authors.lastname: Hinoda
authors.forename: R
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D018925:Chemokines; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051901:Smad4 Protein / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C533449:MIRN183 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D051153:Wnt Proteins; D051176:beta Catenin
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