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Cyclin D1 is a major target of miR-206 in cell differentiation and transformation.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2013 Dec 15; Vol. 12 (24), pp. 3781-90. Date of Electronic Publication: 2013 Oct 08. - Publication Year :
- 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.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma metabolism
Cell Line, Transformed
Cell Line, Tumor
Cell Transformation, Neoplastic pathology
Cyclin D1 metabolism
Humans
Lung Neoplasms genetics
Lung Neoplasms metabolism
MicroRNAs genetics
Muscle, Skeletal cytology
Muscle, Skeletal metabolism
Organ Specificity
Cell Differentiation genetics
Cell Transformation, Neoplastic genetics
Cyclin D1 genetics
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 12
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 24107628
- Full Text :
- https://doi.org/10.4161/cc.26674