Mechanistic Aspects of COX-2 Expression in Colorectal Neoplasia

  • Dan A. DixonEmail author
  • Fernando F. Blanco
  • Annalisa Bruno
  • Paola PatrignaniEmail author
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 191)


The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states and a large amount of evidence has demonstrated constitutive COX-2 expression to be a contributing factor promoting colorectal cancer (CRC). Various genetic, epigenetic, and inflammatory pathways have been identified to be involved in the etiology and development of CRC. Alteration in these pathways can influence COX-2 expression at multiple stages of colon carcinogenesis allowing for elevated prostanoid biosynthesis to occur in the tumor microenvironment. In normal cells, COX-2 expression levels are potently regulated at the post-transcriptional level through various RNA sequence elements present within the mRNA 3′ untranslated region (3′UTR). A conserved AU-rich element (ARE) functions to target COX-2 mRNA for rapid decay and translational inhibition through association with various RNA-binding proteins to influence the fate of COX-2 mRNA. Specific microRNAs (miRNAs) bind regions within the COX-2 3′UTR and control COX-2 expression. In this chapter, we discuss novel insights in the mechanisms of altered post-transcriptional regulation of COX-2 in CRC and how this knowledge may be used to develop novel strategies for cancer prevention and treatment.


Adenomatous Polyposis Coli Lynch Syndrome Colon Tumorigenesis T8473C Single Nucleotide Polymorphism Cytoplasmic Stress Granule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Colorectal cancer




Chromosomal instability


Adenomatous polyposis coli


Familial adenomatous polyposis


Epidermal growth factor


Transforming growth factor












Nonsteroidal anti-inflammatory drugs


Microsomal Prostaglandin E Synthase


15-hydroxyprostaglandin dehydrogenase


Peroxisome proliferator-activated receptor


Rich elements (AREs)




Hu antigen R


T cell intracellular antigen 1


RNA-binding motif protein 3



This work was supported by the National Institutes of Health (R01 CA134609 to D.A. Dixon) and American Cancer Society (RSG-06-122-01-CNE to D.A. Dixon). We apologize to our colleagues for not being able to reference all primary work due to space limitations.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Cancer BiologyUniversity of Kansas Medical CenterKansasUSA
  2. 2.Center of Excellence on Aging (CeSI) and Department of Medicine and AgingG. d’Annunzio University, School of MedicineChietiItaly
  3. 3.Center of Excellence on Aging (CeSI) and Department of Neuroscience and ImagingG. d’Annunzio University, School of MedicineChietiItaly

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