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

Alessandra Alteri, Francesca De Vito, Graziella Messina, Monica Pompili, Attilio Calconi, Paolo Visca, Marcella Mottolese, Carlo Presutti, Milena Grossi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3781-3790
Number of pages10
JournalCell Cycle
Volume12
Issue number24
DOIs
Publication statusPublished - Dec 15 2013

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Keywords

  • Cell proliferation
  • Cell transformation
  • Cyclin D1
  • miR-206
  • Myogenic differentiation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Alteri, A., De Vito, F., Messina, G., Pompili, M., Calconi, A., Visca, P., Mottolese, M., Presutti, C., & Grossi, M. (2013). Cyclin D1 is a major target of miR-206 in cell differentiation and transformation. Cell Cycle, 12(24), 3781-3790. https://doi.org/10.4161/cc.26674