miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1

Silvia Galardi, Neri Mercatelli, Ezio Giorda, Simone Massalini, Giovanni Vanni Frajese, Silvia Anna Ciafrè, Maria Giulia Farace

Research output: Contribution to journalArticle

Abstract

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of several types of cancers. Here we show that miR-221 and miR-222, encoded in tandem on chromosome X, are overexpressed in the PC3 cellular model of aggressive prostate carcinoma, as compared with LNCaP and 22Rv1 cell line models of slowly growing carcinomas. In all cell lines tested, we show an inverse relationship between the expression of miR-221 and miR-222 and the cell cycle inhibitor p27Kip1. We recognize two target sites for the microRNAs in the 3′ untranslated region of p27 mRNA, and we show that miR-221/222 ectopic overexpression directly results in p27 downregulation in LNCaP cells. In those cells, we demonstrate that the ectopic overexpression of miR-221/222 strongly affects their growth potential by inducing a G1 to S shift in the cell cycle and is sufficient to induce a powerful enhancement of their colony-forming potential in soft agar. Consistently, miR-221 and miR-222 knock-down through antisense LNA oligonucleotides increases p27 Kip1 in PC3 cells and strongly reduces their clonogenicity in vitro. Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27Kip1, and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27Kip1 down-regulation.

Original languageEnglish
Pages (from-to)23716-23724
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number32
DOIs
Publication statusPublished - Aug 10 2007

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this