A common single-nucleotide polymorphism in cyclooxygenase-2 disrupts microRNA-mediated regulation.
A common single-nucleotide polymorphism in cyclooxygenase-2 disrupts microRNA-mediated regulation.
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DOI：
10.1038/onc.2011.349
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发表时间：
2012-03-22
期刊：
影响因子：
8
通讯作者：
Dixon, D. A.
中科院分区：
文献类型：
--
作者：
Moore, A. E.;Young, L. E.;Dixon, D. A.
Elevated expression of the prostaglandin synthase cyclooxygenase-2 (COX-2) is commonly observed in many chronic inflammatory diseases and cancer. However, the mechanisms allowing for pathogenic COX-2 overexpression are largely unknown. The gene for COX-2 (PTGS2) carries a common single-nucleotide polymorphism (SNP) at position 8473 (T8473C), in exon 10 that is associated with diseases in which COX-2 overexpression is a contributing factor. We demonstrate that the T8473C SNP resides within a region that targets COX-2 mRNA for degradation through microRNA-mediated regulation. miR-542-3p was identified to bind transcripts derived from the 8473T allele and promote mRNA decay. By contrast, the presence of the variant 8473C allele interfered with miR-542-3p binding, allowing for mRNA stabilization, and this effect was rescued using a mutated miR-542-3p at the respective 8473 site. Colon cancer cells and tissue displayed COX-2 mRNA levels that were dependent on T8473C allele dosage, and allele-specific expression of COX-2 was observed to be a contributing factor promoting COX-2 overexpression. These findings provide a novel molecular explanation underlying disease susceptibility associated with COX-2 T8473C SNP, and identify it as a potential marker for identifying cancer patients best served through selective COX-2 inhibition.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-09-0788
发表时间：
2010-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Menter DG;Schilsky RL;DuBois RN
通讯作者：
DuBois RN
影响因子：
4.8
作者：
Dixon, DA;Kaplan, CD;Prescott, SM
通讯作者：
Prescott, SM
影响因子：
2.8
作者：
Gong, Zhihong;Bostick, Roberd M.;Hebert, James R.
通讯作者：
Hebert, James R.
影响因子：
11.5
作者：
Langsenlehner, U;Yazdani-Biuki, B;Krippl, P
通讯作者：
Krippl, P