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).

le Sage, C., Nagel, R., Egan, D., Schrier, M., Mesman, E., Mangiola, A., et al. (2007). Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO JOURNAL, 26(15), 3699-3708 [10.1038/sj.emboj.7601790].

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

MERCATELLI, NERI;CIAFRE', SILVIA ANNA;FARACE, MARIA GIULIA;
2007-08-08

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).
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Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13
English
Con Impact Factor ISI
Flow Cytometry; Cell Line, Tumor; 3T3 Cells; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27; Reverse Transcriptase Polymerase Chain Reaction; Mice; Neoplasms; MicroRNAs; Animals; Humans
le Sage, C., Nagel, R., Egan, D., Schrier, M., Mesman, E., Mangiola, A., et al. (2007). Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO JOURNAL, 26(15), 3699-3708 [10.1038/sj.emboj.7601790].
le Sage, C; Nagel, R; Egan, D; Schrier, M; Mesman, E; Mangiola, A; Anile, C; Maira, G; Mercatelli, N; Ciafre', Sa; Farace, Mg; Agami, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/9178
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