The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27(Kip1) mRNA. This leads to higher levels of p27(Kip1) in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma.

Galardi, S., Petretich, M., Pinna, G., D'Amico, S., Loreni, F., Michienzi, A., et al. (2016). CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation. SCIENTIFIC REPORTS, 6, 25219 [10.1038/srep25219].

CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation

GALARDI, SILVIA;LORENI, FABRIZIO;MICHIENZI, ALESSANDRO;CIAFRE', SILVIA ANNA
2016-05-04

Abstract

The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity. Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation of poly-A tail and the subsequent translation of p27(Kip1) mRNA. This leads to higher levels of p27(Kip1) in the cell, in turn significantly inhibiting cell proliferation, and confers to CPEB1 a potential value as a tumor suppressor in Glioblastoma.
4-mag-2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
Con Impact Factor ISI
Galardi, S., Petretich, M., Pinna, G., D'Amico, S., Loreni, F., Michienzi, A., et al. (2016). CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation. SCIENTIFIC REPORTS, 6, 25219 [10.1038/srep25219].
Galardi, S; Petretich, M; Pinna, G; D'Amico, S; Loreni, F; Michienzi, A; Groisman, I; Ciafre', Sa
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/165395
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