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Publication : The microRNA 424/503 cluster reduces CDC25A expression during cell cycle arrest imposed by transforming growth factor β in mammary epithelial cells.

First Author  Llobet-Navas D Year  2014
Journal  Mol Cell Biol Volume  34
Issue  23 Pages  4216-31
PubMed ID  25266660 Mgi Jnum  J:224323
Mgi Id  MGI:5662023 Doi  10.1128/MCB.00611-14
Citation  Llobet-Navas D, et al. (2014) The microRNA 424/503 cluster reduces CDC25A expression during cell cycle arrest imposed by transforming growth factor beta in mammary epithelial cells. Mol Cell Biol 34(23):4216-31
abstractText  Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor beta (TGF-beta) 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-beta. Mechanistically, we showed that after TGF-beta 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-beta/miR-424(322)/503 axis is part of the mechanism that regulates the proliferation of hormone receptor-positive (HR(+)) mammary epithelial cells in vivo.
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