MicroRNA-21 inhibits p57Kip2 expression in prostate cancer

Sweta Mishra, Chun Lin Lin, Tim H.M. Huang, Hakim Bouamar, Lu Zhe Sun

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background: p57Kip2, 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 p57Kip2 protein has been frequently observed in pancreatic, lung, breast, bladder, gastrointestinal tract and prostate cancers. However, p57Kip2 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 p57Kip2 in prostate cancer. Findings: We observed a significant negative correlation between the expression of p57Kip2 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 p57Kip2 mRNA and protein levels in prostate cancer cells. Conversely, inhibition of endogenous miR-21 by an anti-miR-21 inhibitor strongly induced p57Kip2 expression. Furthermore, we found that knockdown of p57Kip2 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 p57Kip2 expression by targeting the coding region of the gene and is also able to attenuate p57Kip2 mediated functional responses. This is the first report demonstrating that p57Kip2 is a novel target of miR-21 in prostate cancer and revealing a novel oncogenic function of this microRNA.

Original languageEnglish (US)
Article number212
JournalMolecular Cancer
Volume13
Issue number1
DOIs
StatePublished - Sep 12 2014

Keywords

  • microRNA-21 and prostate cancer
  • p57

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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