title: MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells.
abstract: MicroRNAs are small noncoding RNA species, some of which are playing important roles in cell differentiation. However, the level of participations of microRNAs in epithelial cell differentiation is largely unknown. Here, utilizing an epithelial differentiation model with T84 cells, we demonstrate that miR-338-3p and miR-451 contribute to the formation of epithelial basolateral polarity by facilitating translocalization of beta1 integrin to the basolateral membrane. Among 250 microRNAs screened in this study, the expression levels of four microRNAs (miR-33a, 210, 338-3p and 451) were significantly elevated in the differentiated stage of T84 cells, when epithelial cell polarity was established. To investigate the involvement of these microRNAs in terms of epithelial cell polarity, we executed loss-of- and gain-of-function analyses of these microRNAs. The blockade of endogenous miR-338-3p or miR-451 via each microRNA-specific antisense oligonucleotides inhibited the translocalization of beta1 integrin to the basolateral membrane, whereas inhibition of miR-210 or miR-33a had no effect on it. On the other hand, simultaneous transfection of synthetic miR-338-3p and miR-451 accelerated the translocalization of beta1 integrin to the basolateral membrane, although the introduction of individual synthetic microRNAs exhibited no effect. Therefore, we concluded that both miR-338-3p and miR-451 are necessary for the development of epithelial cell polarity.
authors.affiliation: Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Masahito
authors.initials: M
authors.lastname: Oku
authors.forename: Yukako
authors.initials: Y
authors.lastname: Imanaka
authors.forename: Ryo
authors.initials: R
authors.lastname: Kunimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Kazuya
authors.initials: K
authors.lastname: Terasawa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C531201:MIRN451 microRNA, human; D035683:MicroRNAs