Abstract
Estrogen receptor beta 1 (ER beta 1) downregulation occurs in many breast cancers, but the responsible molecular mechanisms remain unclear. Here, we report that levels of ER beta 1 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 ER beta 1 mRNA and protein. Inhibition of miR-92 in MCF-7 cells increased ER beta 1 expression in a dose-dependent manner, whereas miR-92 overexpression led to ER beta 1 downregulation. Reporter constructs containing candidate miR-92 binding sites in the 3'-untranslated region (UTR) of ER beta 1 suggested by bioinformatics analysis confirmed that miR-92 downregulated ER beta 1 via direct targeting of its 3'-UTR. Our results define a potentially important mechanism for downregulation of ER beta 1 expression in breast cancer. Cancer Res; 70(11); 4778-84. (C) 2010 AACR.