Estrogen Receptor β1 Expression Is Regulated by miR-92 in Breast Cancer

被引：90

作者：

Al-Nakhle, Hakeemah ^{[1
]}

Burns, Philip A. ^{[1
]}

Cummings, Michele ^{[1
]}

Hanby, Andrew M. ^{[1
]}

Hughes, Thomas A. ^{[1
]}

Satheesha, Sampoorna ^{[1
]}

Shaaban, Abeer M. ^{[1
]}

Smith, Laura ^{[1
]}

Speirs, Valerie ^{[1
]}

机构：

[1] Univ Leeds, Leeds Inst Mol Med, Leeds LS9 7TF, W Yorkshire, England

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

关键词：

MICRORNA EXPRESSION; CELL-LINES; ER-BETA; MIR-17-92; CLUSTER; EPITHELIAL-CELLS; ALPHA; GROWTH; METHYLATION; ISOFORMS; RNA;

D O I：

10.1158/0008-5472.CAN-09-4104

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：4778 / 4784

页数：7

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