title: A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance.
abstract: In this report, we have shown that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice than in virgin mice. Furthermore, miR146b levels were significantly higher in mouse mammary glands exposed to the sex hormones, estrogen and progesterone, compared with those of untreated control animals. Pregnancy-derived primary mouse mammary epithelial cells in which miR146b was knocked down showed a significant reduction in the number of hollow acinar organoid structures formed on three-dimensional Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures, whereas solid organoid structures are derived from stem cells. Among several miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cell death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that during pregnancy miR146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating STAT3β.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Hanan S
authors.initials: HS
authors.lastname: Elsarraj
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Kelli
authors.initials: K
authors.lastname: Valdez
authors.forename: Martha
authors.initials: M
authors.lastname: Carletti
authors.forename: Sally M
authors.initials: SM
authors.lastname: Salah
authors.forename: Monica
authors.initials: M
authors.lastname: Raimo
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Philippe
authors.initials: P
authors.lastname: Prochasson
authors.forename: Uddalak
authors.initials: U
authors.lastname: Bharadwaj
authors.forename: David J
authors.initials: DJ
authors.lastname: Tweardy
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
authors.forename: Fariba
authors.initials: F
authors.lastname: Behbod
mesh_terms: D000818:Animals; D002364:Caseins / Q000096:biosynthesis; D004967:Estrogens / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy / Q000502:physiology*; D011374:Progesterone / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D002364:Caseins; D004967:Estrogens; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D050796:STAT3 Transcription Factor; D011374:Progesterone
keywords: Alveolar Progenitors; MicroRNA-146b; STAT3