miR-206, a member of the so-called myomiR family, is largely acknowledged as a specific, positive regulator of skeletal muscle differentiation. A growing body of evidence also suggests a tumor suppressor function for miR-206, as it is frequently downregulated in various types of cancers. In this study, we show that miR-206 directly targets cyclin D1 and contributes to the regulation of CCND1 gene expression in both myogenic and non-muscle, transformed cells. We demonstrate that miR-206, either exogenous or endogenous, reduces cyclin D1 levels and proliferation rate in C2C12 cells without promoting differentiation, and that miR-206 knockdown in terminally differentiated C2C12 cells leads to cyclin D1 accumulation in myotubes, indicating that miR-206 might be involved in the maintenance of the post-mitotic state. Targeting of cyclin D1 might also account, at least in part, for the tumor-suppressor activity suggested for miR-206 in previous studies. Accordingly, the analysis of neoplastic and matched normal lung tissues reveals that miR-206 downregulation in lung tumors correlates, in most cases, with higher cyclin D1 levels. Moreover, gain-of-function experiments with cancer-derived cell lines and with in vitro transformed cells indicate that miR-206-mediated cyclin D1 repression is directly coupled to growth inhibition. Altogether, our data highlight a novel activity for miR-206 in skeletal muscle differentiation and identify cyclin D1 as a major target that further strengthens the tumor suppressor function proposed for miR-206.

Cyclin D1 is a major target of miR-206 in cell differentiation and transformation / Alteri, Alessandra; Francesca De, Vito; Graziella, Messina; Pompili, Monica; Calconi, Attilio; Paolo, Visca; Marcella, Mottolese; Presutti, Carlo; Grossi, Milena. - In: CELL CYCLE. - ISSN 1538-4101. - STAMPA. - 12:24(2013), pp. 3781-3790. [10.4161/cc.26674]

Cyclin D1 is a major target of miR-206 in cell differentiation and transformation

ALTERI, ALESSANDRA;POMPILI, Monica;CALCONI, Attilio;PRESUTTI, Carlo;GROSSI, Milena
2013

Abstract

miR-206, a member of the so-called myomiR family, is largely acknowledged as a specific, positive regulator of skeletal muscle differentiation. A growing body of evidence also suggests a tumor suppressor function for miR-206, as it is frequently downregulated in various types of cancers. In this study, we show that miR-206 directly targets cyclin D1 and contributes to the regulation of CCND1 gene expression in both myogenic and non-muscle, transformed cells. We demonstrate that miR-206, either exogenous or endogenous, reduces cyclin D1 levels and proliferation rate in C2C12 cells without promoting differentiation, and that miR-206 knockdown in terminally differentiated C2C12 cells leads to cyclin D1 accumulation in myotubes, indicating that miR-206 might be involved in the maintenance of the post-mitotic state. Targeting of cyclin D1 might also account, at least in part, for the tumor-suppressor activity suggested for miR-206 in previous studies. Accordingly, the analysis of neoplastic and matched normal lung tissues reveals that miR-206 downregulation in lung tumors correlates, in most cases, with higher cyclin D1 levels. Moreover, gain-of-function experiments with cancer-derived cell lines and with in vitro transformed cells indicate that miR-206-mediated cyclin D1 repression is directly coupled to growth inhibition. Altogether, our data highlight a novel activity for miR-206 in skeletal muscle differentiation and identify cyclin D1 as a major target that further strengthens the tumor suppressor function proposed for miR-206.
2013
cell proliferation; cell transformation; cyclin d1; mir-206; myogenic differentiation
01 Pubblicazione su rivista::01a Articolo in rivista
Cyclin D1 is a major target of miR-206 in cell differentiation and transformation / Alteri, Alessandra; Francesca De, Vito; Graziella, Messina; Pompili, Monica; Calconi, Attilio; Paolo, Visca; Marcella, Mottolese; Presutti, Carlo; Grossi, Milena. - In: CELL CYCLE. - ISSN 1538-4101. - STAMPA. - 12:24(2013), pp. 3781-3790. [10.4161/cc.26674]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/543785
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