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Author Notes:

Address correspondence to Jin-Tang Dong; Email: j.dong@emory.edu

We thank Peng Guo of the Xi'an Jiaotong University School of Medicine for advice, Yuanli Chen and Yunfan Yang of Nankai University for their comments on the manuscript and technological assistance during this study, and Lori King and Frederick Dong for editing the manuscript.

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Research Funding:

This work was supported by grant 81130044 from the National Natural Science Foundation of China and grant R01CA171189 from the National Cancer Institute, National Institutes of Health.

KLF5 Activates MicroRNA 200 Transcription To Maintain Epithelial Characteristics and Prevent Induced Epithelial-Mesenchymal Transition in Epithelial Cells

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Journal Title:

Molecular and Cellular Biology

Volume:

Volume 33, Number 24

Publisher:

, Pages 4919-4935

Type of Work:

Article | Final Publisher PDF

Abstract:

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 β (TGF-β)- 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-β 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-β and EGF treatment, and ectopic expression of KLF5 attenuated TGF-β- 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.

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© 2013, American Society for Microbiology. All Rights Reserved.

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