title: Estrogen receptor β expression induces changes in the microRNA pool in human colon cancer cells.
abstract: There is epidemiological, animal and in vitro evidence that estrogen receptor β (ERβ) can mediate protective effects against colon cancer, but the mechanism is not completely understood. Previous research has indicated critical pathways whereby ERβ acts in an antitumorigenic fashion. In this study, we investigate ERβ's impact on the microRNA (miRNA) pool in colon cancer cells using large-scale genomic approaches, bioinformatics and focused functional studies. We detect and confirm 27 miRNAs to be significantly changed following ERβ expression in SW480 colon cancer cells. Among these, the oncogenic miR-17-92 cluster and miR-200a/b are strongly downregulated. Using target prediction and anticorrelation to gene expression data followed by focused mechanistic studies, we demonstrate that repression of miR-17 is a secondary event following ERβ's downregulatory effect on MYC. We show that re-introduction of miR-17 can reverse the antiproliferative effects of ERβ. The repression of miR-17 also influences cell death upon DNA damage and mediates regulation of NCOA3 (SRC-3) and CLU in colon cancer cells. We further determine that the downregulation of miR-200a/b mediates increased ZEB1 while decreasing E-cadherin levels in ERβ-expressing colon cancer cells. Changes in these genes correspond to significant alterations in morphology and migration. Our work contributes novel data of ERβ and miRNA in the colon. Elucidating the mechanism of ERβ and biomarkers of its activity has significant potential to impact colon cancer prevention and treatment.
authors: Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA.
authors: Karin
authors: K
authors: Edvardsson
authors: Trang
authors: T
authors: Nguyen-Vu
authors: Sharanya M
authors: SM
authors: Kalasekar
authors: Fredrik
authors: F
authors: Pontén
authors: Jan-Åke
authors: JÅ
authors: Gustafsson
authors: Cecilia
authors: C
authors: Williams
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002465:Cell Movement; D048430:Cell Shape; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D047629:Estrogen Receptor beta; D018398:Homeodomain Proteins; C524941:MIRN17 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3