title: Epithelial cell differentiation regulated by MicroRNA-200a in mammary glands.
abstract: Mammary gland epithelial cells undergo periodic cycles of proliferation, differentiation, and involution. Many studies have reported that miRNAs, which are small, non-coding RNAs, influence a variety of biological processes during posttranscriptional regulation. Here, we found that one miRNA, miR-200a, was relatively highly expressed in epithelial cell-rich organs such as mammary glands, lung, and kidney in mice. In mammary glands, miR-200a expression increased during mid-pregnancy through lactation; its expression was stimulated by lactogenic hormone treatment of mammary epithelial cells. Lactogenic hormone also induced the expression of milk protein ß-casein mRNA (a marker of cell differentiation) and E-cadherin mRNA (a marker of epithelial cells). However, knockdown of miR-200a prevented increases in ß-casein and E-cadherin mRNA expression. Protein analysis revealed that E-cadherin signal was decreased and ZEB1 (a marker of EMT) was increased following miR-200a knockdown. Finally, in a three-dimensional culture system modeling lumen-containing mammary ducts, miR-200a knockdown decreased the cavity formation rate and suppressed claudin-3 and par-6b expression, indicating reduced epithelial cell polarity. These observations suggest that miR-200a is important for maintaining the epithelial cell phenotype, which contributes to lactogenic hormone induction of cellular differentiation in mammary glands.
authors.affiliation: Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan. nagaokak@cc.tuat.ac.jp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagaoka
authors.forename: Haolin
authors.initials: H
authors.lastname: Zhang
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Taya
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse