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PMID: 17627278 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.

The EMBO journal ·Vol. 26 ·No. 15 ·2007-08-08 ·Pages 3699-708

le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafrè SA, Farace MG, Agami R

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 p27(Kip1), 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 p27(Kip1) levels and continuous proliferation. Interestingly, high levels of miR-221&222 appear in glioblastomas and correlate with low levels of p27(Kip1) protein. Thus, deregulated expression of miR-221&222 promotes cancerous growth by inhibiting the expression of p27(Kip1).

MeSH Terms
3T3 Cells Animals Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase Inhibitor p27/physiology Flow Cytometry Humans Mice MicroRNAs/physiology Neoplasms/pathology Reverse Transcriptase Polymerase Chain Reaction
Chemicals
MicroRNAs Cyclin-Dependent Kinase Inhibitor p27
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
le Sage Carlos
Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Nagel Remco
Egan David A
Schrier Mariette
Mesman Elly
Mangiola Annunziato
Anile Corrado
Maira Giulio
Mercatelli Neri
Ciafrè Silvia Anna
Farace Maria Giulia
Agami Reuven
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601790
Published
2007-08-08
Epub
2007-00-12
Pages
3699-708
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1949005
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601790 PMC Full Text View journal details
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