Regulation of the p27Kip1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation

Carlos Le Sage, Remco Nagel, David A. Egan, Mariette Schrier, Elly Mesman, Annunziato Mangiola, Corrado Anile, Giulio Maira, Neri Mercatelli, Silvia Anna Ciafrè, Maria Giulia Farace, Reuven Agami

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein coding genes. Patterns of misexpression of miRNAs in cancer suggest key functions of miRNAs in tumorigenesis. However, current bioinformatics tools do not entirely support the identification and characterization of the mode of action of such miRNAs. Here, we used a novel functional genetic approach and identified miR-221 and miR-222 (miR-221&222) as potent regulators of p27Kip1, a cell cycle inhibitor and tumor suppressor. Using miRNA inhibitors, we demonstrate that certain cancer cell lines require high activity of miR-221&222 to maintain low p27Kip1 levels and continuous proliferation. Interestingly, high levels of miR-221&222 appear in glioblastomas and correlate with low levels of p27Kip1 protein. Thus, deregulated expression of miR-221&222 promotes cancerous growth by inhibiting the expression of p27Kip1.

Original languageEnglish
Pages (from-to)3699-3708
Number of pages10
JournalEMBO Journal
Volume26
Issue number15
DOIs
Publication statusPublished - Aug 8 2007

Keywords

  • Cancer
  • Genetic screen
  • miRNA
  • p27

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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