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Molecular and Cellular Biology, July 2009, p. 3783-3790, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.01875-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

miR-22 Inhibits Estrogen Signaling by Directly Targeting the Estrogen Receptor {alpha} mRNA{triangledown} ,{dagger}

Deo Prakash Pandey and Didier Picard*

Département de Biologie Cellulaire, Université de Genève, Sciences III, 30, quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland

Received 10 December 2008/ Returned for modification 28 January 2009/ Accepted 24 April 2009

Estrogen receptor {alpha} (ER{alpha}) is a ligand-regulated transcription factor with a broad range of physiological functions and one of the most important classifiers in breast cancer. MicroRNAs (miRNAs) are small noncoding RNAs that have emerged as important regulators of gene expression in a plethora of physiological and pathological processes. Upon binding the 3' untranslated region (UTR) of target mRNAs, miRNAs typically reduce their stability and/or translation. The ER{alpha} mRNA has a long 3' UTR of about 4.3 kb which has been reported to reduce mRNA stability and which bears evolutionarily conserved miRNA target sites, suggesting that it might be regulated by miRNAs. We have performed a comprehensive and systematic assessment of the regulatory role of all miRNAs that are predicted to target the 3' UTR of the ER{alpha} mRNA. We found that miR-22 represses ER{alpha} expression most strongly and by directly targeting the ER{alpha} mRNA 3' UTR. Of the three predicted miR-22 target sites in the 3' UTR, the evolutionarily conserved one is the primary target. miR-22 overexpression leads to a reduction of ER{alpha} levels, at least in part by inducing mRNA degradation, and compromises estrogen signaling, as exemplified by its inhibitory impact on the ER{alpha}-dependent proliferation of breast cancer cells.

* Corresponding author. Mailing address: Département de Biologie Cellulaire, Université de Genève, Sciences III, 30, quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Phone: 41 22 379 6813. Fax: 41 22 379 6928. E-mail: didier.picard{at}unige.ch

{triangledown} Published ahead of print on 4 May 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, July 2009, p. 3783-3790, Vol. 29, No. 13
0270-7306/09/$08.00+0     doi:10.1128/MCB.01875-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Castellano, L., Giamas, G., Jacob, J., Coombes, R. C., Lucchesi, W., Thiruchelvam, P., Barton, G., Jiao, L. R., Wait, R., Waxman, J., Hannon, G. J., Stebbing, J. (2009). The estrogen receptor-{alpha}-induced microRNA signature regulates itself and its transcriptional response. Proc. Natl. Acad. Sci. USA 106: 15732-15737 [Abstract] [Full Text]  


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