Nucleic Acids Research Advance Access originally published online on April 22, 2009
Nucleic Acids Research 2009 37(11):3821-3827; doi:10.1093/nar/gkp255
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Nucleic Acids Research, 2009, Vol. 37, No. 11 3821-3827
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells
1Department of Nanobio Drug Discovery, 2Department of Pharmacogenomics and 3Department of Systems Bioscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan
*To whom correspondence should be addressed. Tel: +81 75 753 9556; Fax: +81 75 753 9557; Email: kazushmz{at}pharm.kyoto-u.ac.jp
Received December 9, 2008. Revised April 6, 2009. Accepted April 6, 2009.
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 β1 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 β1 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 β1 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.