title: Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer.
abstract: Progesterone receptors (PRs) mediate response to progestins in the normal breast and breast cancer. To determine if liganded PR regulate microRNAs (miRNAs) as a component of their action, we profiled mature miRNA levels following progestin treatment. Indeed, 28 miRNAs are significantly altered by 6h of progestin treatment. Many progestin-responsive genes are putative targets of progestin-regulated miRNAs; for example, progestin treatment decreases miR-29, thereby relieving repression of one of its direct targets, the gene encoding ATPase, Na(+)/K(+) transporting, beta 1 polypeptide (ATP1B1). Thus, liganded PR regulates ATP1B1 through sites in the promoter and the 3'UTR, to achieve maximal tight hormonal regulation of ATP1B1 protein via both transcriptional and translational control. We find that ATP1B1 serves to limit migration and invasion in breast cancer cells. Lastly, we demonstrate that PR itself is regulated by a progestin-upregulated miRNA, miR-513a-5p, providing a novel mechanism for tight control of PR protein expression.
authors.affiliation: Department of Pathology, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Cochrane
authors.affiliation: Department of Medicine, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: Britta M
authors.initials: BM
authors.lastname: Jacobsen
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Connaghan
authors.affiliation: Department of Pathology, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Howe
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Bain
authors.affiliation: Department of Pathology, University of Colorado Denver Anschutz Medical Campus, Denver, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Richer
mesh_terms: D020413:3' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D011980:Receptors, Progesterone / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C503551:ATP1B1 protein, human; D035683:MicroRNAs; D011372:Progestins; D011980:Receptors, Progesterone; D008156:Luciferases; D000254:Sodium-Potassium-Exchanging ATPase