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. |