title: MicroRNA-21 inhibits p57Kip2 expression in prostate cancer.
abstract: BACKGROUND
  p57(Kip2), a cyclin-dependent kinase inhibitor, is considered to be a candidate tumor suppressor gene that has been implicated in Beckwith-Wiedemann syndrome and sporadic cancers. In addition, decreased expression of p57(Kip2) protein has been frequently observed in pancreatic, lung, breast, bladder, gastrointestinal tract and prostate cancers. However, p57(Kip2) gene mutations are rare in these cancers suggesting that other unknown mechanisms might be at play in reducing its expression. The aim of this study was to investigate the molecular mechanism of down-regulation of p57(Kip2) in prostate cancer.
  
  
  RESULTS
  We observed a significant negative correlation between the expression of p57(Kip2) and microRNA-21 (miR-21) in prostate cancer samples and after androgen deprivation with castration in the CWR22 human prostate cancer xenograft model. We report that miR-21 targeted the coding region and decreased p57(Kip2) mRNA and protein levels in prostate cancer cells. Conversely, inhibition of endogenous miR-21 by an anti-miR-21 inhibitor strongly induced p57(Kip2) expression. Furthermore, we found that knockdown of p57(Kip2) reversed the effects of the anti-miR-21 inhibitor on cell migration and anchorage-independent cell growth.
  
  
  CONCLUSIONS
  Our results indicate that miR-21 is able to downregulate p57(Kip2) expression by targeting the coding region of the gene and is also able to attenuate p57(Kip2) mediated functional responses. This is the first report demonstrating that p57(Kip2) is a novel target of miR-21 in prostate cancer and revealing a novel oncogenic function of this microRNA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Mishra
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.forename: Hakim
authors.initials: H
authors.lastname: Bouamar
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7762, San Antonio, TX 78229-3900, USA. sunl@uthscsa.edu.
authors.forename: Lu-Zhe
authors.initials: LZ
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: C410798:AR protein, human; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen