MiR-205 exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cε

Paolo Gandellini, Marco Folini, Nicole Longoni, Marzia Pennati, Mara Binda, Maurizio Colecchia, Roberto Samoni, Rosanna Supino, Roberta Moretti, Patrizia Limonta, Rlccardo Valdagni, Maria Grazia Daidone, Nadia Zaffaroni

Research output: Contribution to journalArticle

Abstract

Limited information is available concerning the expression and role of mieroRNAs in prostate cancer. In this study, we investigated the involvement of miR-205 in prostate carcinogenesis. Significantly lower miR-205 expression levels were found in cancer than in normal prostate cell lines as well as in tumor compared with matched normal prostate tissues, with a particularly pronounced reduction in carcinomas from patients with local-regionally disseminated disease. Restoring the expression of miR-205 in prostate cancer cells resulted in cell rearrangements consistent with a mesenchymal- to-epithelial transition, such as up-regulation of E-cadherin and reduction of cell locomotion and invasion, and in the down-regulation of several oncogenes known to be involved in disease progression (i.e., interleukin 6, caveolin-1, EZH2). Our evidence suggests that these events are driven by the concurrent repression of specific predicted miR-205 targets, namely N-chimaerin, ErbB3, E2F1, E2F5, ZEB2, and protein kinase Ce. Strikingly, the latter seemed to play a direct role in regulating epithelial-to-mesenchymal transition. In fact, its down-regulation led to a cell phenotype largely reminiscent of that of cells ectopically expressing miR-205.Overall, we showed for the first time that miR-205 exerts a tumor- suppressive effect in human prostate by counteracting epithelial-to-mesenchymal transition and reducing cell migration/invasion, at least in part through the down- regulation of protein kinase Cε.

Original languageEnglish
Pages (from-to)2287-2295
Number of pages9
JournalCancer Research
Volume69
Issue number6
DOIs
Publication statusPublished - Mar 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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