Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer.
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.
Al-Nakhle
Hakeemah
H
Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.
Burns
Philip A
PA
Cummings
Michele
M
Hanby
Andrew M
AM
Hughes
Thomas A
TA
Satheesha
Sampoorna
S
Shaaban
Abeer M
AM
Smith
Laura
L
Speirs
Valerie
V
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
D020413:3' Untranslated Regions; D047629:Estrogen Receptor beta; D035683:MicroRNAs; D013629:Tamoxifen; D004958:Estradiol