title: KLF5 activates microRNA 200 transcription to maintain epithelial characteristics and prevent induced epithelial-mesenchymal transition in epithelial cells.
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.
authors.affiliation: Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Baotong
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Siyuan
authors.initials: S
authors.lastname: Xia
authors.forename: Changsheng
authors.initials: C
authors.lastname: Xing
authors.forename: Xinpei
authors.initials: X
authors.lastname: Ci
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Ranran
authors.initials: R
authors.lastname: Zhao
authors.forename: Sha
authors.initials: S
authors.lastname: Tian
authors.forename: Gui
authors.initials: G
authors.lastname: Ma
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D063646:Carcinogenesis; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor