The MicroRNA 424/503 Cluster Reduces CDC25A Expression during Cell Cycle Arrest Imposed by Transforming Growth Factor   in Mammary Epithelial Cells

D. Llobet-Navas, R. Rodriguez-Barrueco, J. de la Iglesia-Vicente, M. Olivan, V. Castro, L. Saucedo-Cuevas, N. Marshall, P. Putcha, M. Castillo-Martin, E. Bardot, E. Ezhkova, A. Iavarone, C. Cordon-Cardo, J. M. Silva

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Samenvatting

© 2014, American Society for Microbiology. Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signaling. Here, we expanded our finding to demonstrate that miR-424(322)/503 is an integral component of the cell cycle arrest mediated by TGF-β. Mechanistically, we showed that after TGF-β exposure, increased levels of miR-424(322)/503 reduce the expression of the cell cycle regulator CDC25A. miR- 424(322)/503-dependent posttranscriptional downregulation of CDC25A cooperates with previously described transcriptional repression of the CDC25A promoter and proteasome-mediated degradation to reduce the levels of CDC25A expression and to induce cell cycle arrest. We also provide evidence that the TGF-β/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR + ) mammary epithelial cells in vivo.
Originele taal-2English
Pagina's (van-tot)4216-4231
Aantal pagina's16
TijdschriftMolecular and cellular biology
Volume34
Nummer van het tijdschrift23
DOI's
StatusPublished - 1 dec 2014

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