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 / A. Alteri, F. De Vito, G. Messina, M. Pompili, A. Calconi, P. Visca, M. Mottolese, C. Presutti, M. Grossi. - In: CELL CYCLE. - ISSN 1538-4101. - 12:24(2013 Dec 15), pp. 3781-3790.
|Titolo:||Cyclin D1 is a major target of miR-206 in cell differentiation and transformation|
|Parole Chiave:||Cell proliferation; Cell transformation; Cyclin D1; miR-206; Myogenic differentiation|
|Settore Scientifico Disciplinare:||Settore BIO/17 - Istologia|
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||15-dic-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.4161/cc.26674|
|Appare nelle tipologie:||01 - Articolo su periodico|