1. The MicroRNA 424/503 Cluster Reduces CDC25A Expression during Cell Cycle Arrest Imposed by Transforming Growth Factor β in Mammary Epithelial Cells.
- Author
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Llobet-Navas, David, Rodriguez-Barrueco, Ruth, de la Iglesia-Vicente, Janis, Olivan, Mireia, Castro, Veronica, Saucedo-Cuevas, Laura, Marshall, Netonia, Putcha, Preeti, Castillo-Martin, Mireia, Bardot, Evan, Ezhkova, Elena, Iavarone, Antonio, Cordon-Cardo, Carlos, and Silva, Jose M.
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MICRORNA , *CELL cycle , *TRANSFORMING growth factors , *EPITHELIAL cells , *APOPTOSIS , *SOMATOMEDIN - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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