title: Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs de novo lipogenesis.
abstract: Profiling of RNA from mouse mammary epithelial cells (MECs) isolated on pregnancy day (P)14 and lactation day (L)2 revealed that the majority of differentially expressed microRNA declined precipitously between late pregnancy and lactation. The decline in miR-150, which exhibited the greatest fold-decrease, was verified quantitatively and qualitatively. To test the hypothesis that the decline in miR-150 is crucial for lactation, MEC-specific constitutive miR-150 was achieved by crossing ROSA26-lox-STOP-lox-miR-150 mice with WAP-driven Cre recombinase mice. Both biological and foster pups nursed by bitransgenic dams exhibited a dramatic decrease in survival compared with offspring nursed by littermate control dams. Protein products of predicted miR-150 targets Fasn, Olah, Acaca, and Stat5B were significantly suppressed in MECs of bitransgenic mice with constitutive miR-150 expression as compared with control mice at L2. Lipid profiling revealed a significant reduction in fatty acids synthesized by the de novo pathway in L2 MECs of bitransgenic versus control mice. Collectively, these data support the hypothesis that a synchronized decrease in miRNAs, such as miR-150, at late pregnancy serves to allow translation of targets crucial for lactation.
authors.affiliation: Cancer Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Richard E
authors.identifier: 0000-0003-4850-2248
authors.initials: RE
authors.lastname: Heinz
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Rudolph
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Palani
authors.initials: P
authors.lastname: Ramanathan
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Spoelstra
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Kiel T
authors.initials: KT
authors.lastname: Butterfield
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Patricia G
authors.initials: PG
authors.lastname: Webb
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Beatrice L
authors.initials: BL
authors.lastname: Babbs
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gordon
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.|Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Neville
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China haihua.gu@ucdenver.edu jennifer.richer@ucdenver.edu.|Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Haihua
authors.identifier: 0000-0003-2154-9900
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA haihua.gu@ucdenver.edu jennifer.richer@ucdenver.edu.
authors.forename: Jennifer K
authors.identifier: 0000-0002-9960-0991
authors.initials: JK
authors.lastname: Richer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007774:Lactation / Q000235:genetics* / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D011247:Pregnancy / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse
keywords: Fatty acid synthesis; Lactation; Mammary gland; MicroRNA-150