title: Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.
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).
authors.affiliation: Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Carlos
authors.initials: C
authors.lastname: le Sage
authors.forename: Remco
authors.initials: R
authors.lastname: Nagel
authors.forename: David A
authors.initials: DA
authors.lastname: Egan
authors.forename: Mariette
authors.initials: M
authors.lastname: Schrier
authors.forename: Elly
authors.initials: E
authors.lastname: Mesman
authors.forename: Annunziato
authors.initials: A
authors.lastname: Mangiola
authors.forename: Corrado
authors.initials: C
authors.lastname: Anile
authors.forename: Giulio
authors.initials: G
authors.lastname: Maira
authors.forename: Neri
authors.initials: N
authors.lastname: Mercatelli
authors.forename: Silvia Anna
authors.initials: SA
authors.lastname: Ciafrè
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Farace
authors.forename: Reuven
authors.initials: R
authors.lastname: Agami
mesh_terms: D016475:3T3 Cells; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27