| First Author | Zhang B | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 24 | Pages | 4919-35 |
| PubMed ID | 24126055 | Mgi Jnum | J:206065 |
| Mgi Id | MGI:5547853 | Doi | 10.1128/MCB.00787-13 |
| Citation | Zhang B, et al. (2013) KLF5 activates microRNA 200 transcription to maintain epithelial characteristics and prevent induced epithelial-mesenchymal transition in epithelial cells. Mol Cell Biol 33(24):4919-35 |
| abstractText | KLF5 is an essential basic transcriptional factor that regulates a number of physiopathological processes. In this study, we tested whether and how KLF5 modulates the epithelial-mesenchymal transition (EMT). Using transforming growth factor beta (TGF-beta)- and epidermal growth factor (EGF)-treated epithelial cells as an established model of EMT, we found that KLF5 was downregulated during EMT and that knockdown of KLF5 induced EMT even in the absence of TGF-beta and EGF treatment, as indicated by phenotypic and molecular EMT properties. Array-based screening suggested and biochemical analyses confirmed that the microRNA 200 (miR-200) microRNAs, a group of well-established EMT repressors, were transcriptionally activated by KLF5 via its direct binding to the GC boxes in miR-200 gene promoters. Functionally, overexpression of miR-200 prevented the EMT induced by KLF5 knockdown or by TGF-beta and EGF treatment, and ectopic expression of KLF5 attenuated TGF-beta- and EGF-induced EMT by rescuing the expression of miR-200. In mouse prostates, knockout of Klf5 downregulated the miR-200 family and induced molecular changes indicative of EMT. These findings indicate that KLF5 maintains epithelial characteristics and prevents EMT by transcriptionally activating the miR-200 family in epithelial cells. |
