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: Hakeemah Al-Nakhle, Philip A Burns, Michele Cummings, Andrew M Hanby, Thomas A Hughes, Sampoorna Satheesha, Abeer M Shaaban, Laura Smith, Valerie Speirs
• Journal: Cancer research (Cancer Res) Vol. 70 Issue 11 Pg. 4778-84 (Jun 01 2010) ISSN: 1538-7445 [Electronic] United States
• PMID: 20484043 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright 2010 AACR.

Chemical References

• 3' Untranslated Regions
• Estrogen Receptor beta
• MicroRNAs
• Tamoxifen
• Estradiol

Topics

• 3' Untranslated Regions
• Binding Sites
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Estradiol (pharmacology)
• Estrogen Receptor beta (biosynthesis, genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (antagonists & inhibitors, biosynthesis, genetics, metabolism)
• Tamoxifen (pharmacology)