Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer

Hakeemah Al-Nakhle, Philip A Burns, Michele Cummings, Andrew M Hanby, Thomas A Hughes, Sampoorna Satheesha, Abeer M Shaaban, Laura Smith, Valerie Speirs

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79 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4778-84
Number of pages7
JournalCancer Research
Volume70
Issue number11
DOIs
Publication statusPublished - 1 Jun 2010

Keywords

  • 3' Untranslated Regions
  • Binding Sites
  • Breast Neoplasms
  • Cell Line, Tumor
  • Estradiol
  • Estrogen Receptor beta
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs
  • Tamoxifen
  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.

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  • Cite this

    Al-Nakhle, H., Burns, P. A., Cummings, M., Hanby, A. M., Hughes, T. A., Satheesha, S., Shaaban, A. M., Smith, L., & Speirs, V. (2010). Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer. Cancer Research, 70(11), 4778-84. https://doi.org/10.1158/0008-5472.CAN-09-4104