title: Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer.
abstract: Estrogen receptor beta1 (ERbeta1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ERbeta1 expression are negatively regulated by the microRNA miR-92. Expression analysis in a cohort of primary breast tumors confirmed a significant negative correlation between miR-92 and both ERbeta1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ERbeta1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ERbeta1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ERbeta1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ERbeta1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ERbeta1 expression in breast cancer.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
authors.forename: Hakeemah
authors.initials: H
authors.lastname: Al-Nakhle
authors.forename: Philip A
authors.initials: PA
authors.lastname: Burns
authors.forename: Michele
authors.initials: M
authors.lastname: Cummings
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hanby
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hughes
authors.forename: Sampoorna
authors.initials: S
authors.lastname: Satheesha
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Shaaban
authors.forename: Laura
authors.initials: L
authors.lastname: Smith
authors.forename: Valerie
authors.initials: V
authors.lastname: Speirs
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D020413:3' Untranslated Regions; D047629:Estrogen Receptor beta; D035683:MicroRNAs; D013629:Tamoxifen; D004958:Estradiol