miR-22 Inhibits Estrogen Signaling by Directly Targeting the Estrogen Receptor alpha mRNA Export

@article{citeulike:4484212, abstract = {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. 10.1128/MCB.01875-08}, author = {Pandey, Deo P. and Picard, Didier}, citeulike-article-id = {4484212}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/MCB.01875-08}, citeulike-linkout-1 = {http://mcb.asm.org/content/29/13/3783.abstract}, citeulike-linkout-2 = {http://mcb.asm.org/content/29/13/3783.full.pdf}, citeulike-linkout-3 = {http://mcb.asm.org/cgi/content/abstract/29/13/3783}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/19414598}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=19414598}, day = {1}, doi = {10.1128/MCB.01875-08}, issn = {1098-5549}, journal = {Mol. Cell. Biol.}, keywords = {breast, cancer, era, microrna, mir-18a, mir-22, mir-221}, month = {July}, number = {13}, pages = {3783--3790}, posted-at = {2009-06-02 22:50:53}, priority = {2}, title = {miR-22 Inhibits Estrogen Signaling by Directly Targeting the Estrogen Receptor {alpha} mRNA}, url = {http://dx.doi.org/10.1128/MCB.01875-08}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:4484212 L3 - citeulike-article-id:4484212 N2 - 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. 10.1128/MCB.01875-08 IS - 13 JF - Mol. Cell. Biol. SN - 1098-5549 EP - 3790 TI - miR-22 Inhibits Estrogen Signaling by Directly Targeting the Estrogen Receptor {alpha} mRNA VL - 29 SP - 3783 KW - breast KW - cancer KW - era KW - microrna KW - mir-18a KW - mir-22 KW - mir-221 AU - Pandey, Deo AU - Picard, Didier PY - 2009/07/01/ UR - http://dx.doi.org/10.1128/MCB.01875-08 ER -