title: Suppression of the TGF-β1-induced protein expression of SNAI1 and N-cadherin by miR-199a.
abstract: MicroRNA miR-199a is clustered with miR-214 on chromosome 1 and its expression is up-regulated by various factors that are associated with epithelial-to-mesenchymal transition (EMT), such as a transcriptional repressor Twist1 and transforming growth factor (TGF)-β. miR-199a is either up-regulated or down-regulated in a variety of cancers, although EMT is associated with the progression of cancer. We found here that miR-199a suppressed the translation of SNAI1, a transcriptional repressor that plays a role in EMT, by targeting the sequence within the 3'UTR of the SNAI1 mRNA, and reduced the protein level of SNAI1. miR-199a increased the protein level of claudin-1 in both the TGF-β1-treated and -untreated cells at least partly by decreasing the protein level of SNAI1, a transcriptional repressor for claudin-1. In addition, miR-199a targeted the sequence within the 3'UTR of the N-cadherin mRNA and suppressed the TGF-β1-induced increase in the protein level of N-cadherin in a manner independent of SNAI1. These results indicate that miR-199a suppresses the TGF-β1-induced protein expression of SNAI1 and N-cadherin.
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan; Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan; Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Mizutani
authors.forename: Akihiro
authors.initials: A
authors.lastname: Minami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nobutani
authors.forename: Souichi
authors.initials: S
authors.lastname: Kurita
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D020413:3' Untranslated Regions; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; D062445:Claudin-1; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C531408:mirn199 microRNA, human