Posttranscriptional Regulation of Cyclooxygenase 2

Authors: Lisa E Young Dan A Dixon

Publish Date: 2010/02/24

Volume: 6, Issue: 2, Pages: 60-67

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Abstract

Cyclooxygenase COX2 enzyme catalyzes the ratelimiting step of prostaglandin formation in pathogenic states and overexpression of COX2 occurs at multiple stages of colon carcinogenesis allowing elevated prostaglandin synthesis to occur in the tumor microenvironment In normal cells COX2 expression levels are potently regulated at the posttranscriptional level through various RNA sequence elements present within the mRNA 3 untranslated region 3′UTR A conserved AUrich element functions to target COX2 mRNA for rapid decay and translational inhibition through association with various RNAbinding proteins to influence the fate of COX2 mRNA The 3′UTR contains alternative polyadenylation signals that result in a shortened 3′UTR and loss of regulatory elements Specific microRNAs have been identified to bind regions within the COX2 3′UTR and control COX2 expression Recent evidence demonstrates the functional significance of the COX2 3′UTR and how improper recognition of the 3′UTR can contribute to COX2 overexpression in colorectal cancerThe authors thank David Young for graphics support The authors were funded by grants from the National Institutes of Health R01CA134609 and American Cancer Society RSG0612201CNE They apologize to their colleagues for not being able to reference all primary work owing to space limitations

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