Nucleic Acids Research Advance Access originally published online on March 5, 2009
Nucleic Acids Research 2009 37(8):2584-2595; doi:10.1093/nar/gkp117
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2009, Vol. 37, No. 8 2584-2595
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
RNA |
Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells
Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA
*To whom correspondence should be addressed. Tel: +1 502 852 3668; Fax: +1 502 852 6222; Email: carolyn.klinge{at}louisville.edu
Received December 3, 2008. Revised February 3, 2009. Accepted February 3, 2009.
Select changes in microRNA (miRNA) expression correlate with estrogen receptor 
(ER) expression in breast tumors. miR-21 is higher in ER positive than negative tumors, but no one has examined how estradiol (E2) regulates miR-21 in breast cancer cells. Here we report that E2 inhibits miR-21 expression in MCF-7 human breast cancer cells. The E2-induced reduction in miR-21 was inhibited by 4-hydroxytamoxifen (4-OHT), ICI 182 780 (Faslodex), and siRNA ER indicating that the suppression is ER-mediated. ER and ERβ agonists PPT and DPN inhibited and 4-OHT increased miR-21 expression. E2 increased luciferase activity from reporters containing the miR-21 recognition elements from the 3'-UTRs of miR-21 target genes, corroborating that E2 represses miR-21 expression resulting in a loss of target gene suppression. The E2-mediated decrease in miR-21 correlated with increased protein expression of endogenous miR-21-targets Pdcd4, PTEN and Bcl-2. siRNA knockdown of ER blocked the E2-induced increase in Pdcd4, PTEN and Bcl-2. Transfection of MCF-7 cells with antisense (AS) to miR-21 mimicked the E2-induced increase in Pdcd4, PTEN and Bcl-2. These results are the first to demonstrate that E2 represses the expression of an oncogenic miRNA, miR-21, by activating estrogen receptor in MCF-7 cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Maillot, M. Lacroix-Triki, S. Pierredon, L. Gratadou, S. Schmidt, V. Benes, H. Roche, F. Dalenc, D. Auboeuf, S. Millevoi, et al. Widespread Estrogen-Dependent Repression of microRNAs Involved in Breast Tumor Cell Growth Cancer Res., November 1, 2009; 69(21): 8332 - 8340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Guo Epigenetics of endometriosis Mol. Hum. Reprod., October 1, 2009; 15(10): 587 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Y. W. Bourguignon, C. C. Spevak, G. Wong, W. Xia, and E. Gilad Hyaluronan-CD44 Interaction with Protein Kinase C{epsilon} Promotes Oncogenic Signaling by the Stem Cell Marker Nanog and the Production of MicroRNA-21, Leading to Down-regulation of the Tumor Suppressor Protein PDCD4, Anti-apoptosis, and Chemotherapy Resistance in Breast Tumor Cells J. Biol. Chem., September 25, 2009; 284(39): 26533 - 26546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ribas, X. Ni, M. Haffner, E. A. Wentzel, A. H. Salmasi, W. H. Chowdhury, T. A. Kudrolli, S. Yegnasubramanian, J. Luo, R. Rodriguez, et al. miR-21: An Androgen Receptor-Regulated MicroRNA that Promotes Hormone-Dependent and Hormone-Independent Prostate Cancer Growth Cancer Res., September 15, 2009; 69(18): 7165 - 7169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bhat-Nakshatri, G. Wang, N. R. Collins, M. J. Thomson, T. R. Geistlinger, J. S. Carroll, M. Brown, S. Hammond, E. F. Srour, Y. Liu, et al. Estradiol-regulated microRNAs control estradiol response in breast cancer cells Nucleic Acids Res., August 1, 2009; 37(14): 4850 - 4861. [Abstract] [Full Text] [PDF]
|
|