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Mechanistic Aspects of COX-2 Expression in Colorectal Neoplasia

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Book cover Prospects for Chemoprevention of Colorectal Neoplasia

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 191))

Abstract

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.

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Abbreviations

CRC:

Colorectal cancer

CV:

Cardiovascular

CIN:

Chromosomal instability

APC:

Adenomatous polyposis coli

FAP:

Familial adenomatous polyposis

EGF:

Epidermal growth factor

TGF:

Transforming growth factor

COX:

Cyclooxygenase

PG:

Prostaglandin

(TX)A2 :

Thromboxane

PGI2 :

Prostacyclin

GI:

Gastrointestinal

NSAIDs:

Nonsteroidal anti-inflammatory drugs

mPGES:

Microsomal Prostaglandin E Synthase

15-PGDH:

15-hydroxyprostaglandin dehydrogenase

PPAR:

Peroxisome proliferator-activated receptor

AU:

Rich elements (AREs)

miRNAs:

MicroRNAs

HuR:

Hu antigen R

TIA-1:

T cell intracellular antigen 1

RBM3:

RNA-binding motif protein 3

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Acknowledgments

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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Authors and Affiliations

  1. Department of Cancer Biology, University of Kansas Medical Center, Kansas, KS, 66106, USA

    Dan A. Dixon & Fernando F. Blanco

  2. Center of Excellence on Aging (CeSI) and Department of Medicine and Aging, G. d’Annunzio University, School of Medicine, Via dei, Vestini 31, 66100, Chieti, Italy

    Annalisa Bruno

  3. Center of Excellence on Aging (CeSI) and Department of Neuroscience and Imaging, G. d’Annunzio University, School of Medicine, Via dei, Vestini 31, 66100, Chieti, Italy

    Paola Patrignani

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  1. Dan A. Dixon
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  2. Fernando F. Blanco
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  3. Annalisa Bruno
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  4. Paola Patrignani
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Correspondence to Dan A. Dixon or Paola Patrignani .

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  1. Massachusetts General Hospital, Gastrointestinal Unit, Harvard Medical School, Fruit Street 55, Boston, 02114, Massachusetts, USA

    Andrew T. Chan

  2. BSP-GD-GMA-CVRM, Berlin, S101, 09, 140, Bayer Schering Pharma AG, Müllerstraße 178, Berlin, 13351, Germany

    Elmar Detering

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Dixon, D.A., Blanco, F.F., Bruno, A., Patrignani, P. (2013). Mechanistic Aspects of COX-2 Expression in Colorectal Neoplasia. In: Chan, A., Detering, E. (eds) Prospects for Chemoprevention of Colorectal Neoplasia. Recent Results in Cancer Research, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30331-9_2

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