Posttranscriptional Regulation of Cyclooxygenase 2 Expression in Colorectal Cancer

Overview

Journal Curr Colorectal Cancer Rep

Publisher Springer

Date 2010 Jun 26

PMID 20577575

Citations 34

Authors

Lisa E Young

Dan A Dixon

Affiliations

Soon will be listed here.

Abstract

Cyclooxygenase (COX)-2 enzyme catalyzes the rate-limiting step of prostaglandin formation in pathogenic states, and overexpression of COX-2 occurs at multiple stages of colon carcinogenesis, allowing elevated prostaglandin synthesis to occur in the tumor microenvironment. In normal cells, COX-2 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 AU-rich element 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. 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 COX-2 3'UTR and control COX-2 expression. Recent evidence demonstrates the functional significance of the COX-2 3'UTR and how improper recognition of the 3'UTR can contribute to COX-2 overexpression in colorectal cancer.

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References

Sureban S, Murmu N, Rodriguez P, May R, Maheshwari R, Dieckgraefe B . Functional antagonism between RNA binding proteins HuR and CUGBP2 determines the fate of COX-2 mRNA translation. Gastroenterology. 2007; 132(3):1055-65. DOI: 10.1053/j.gastro.2006.12.031. View

Lee H, Jeong S . Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR. Nucleic Acids Res. 2006; 34(19):5705-14. PMC: 1636482. DOI: 10.1093/nar/gkl698. View

Lopez de Silanes I, Quesada M, Esteller M . Aberrant regulation of messenger RNA 3'-untranslated region in human cancer. Cell Oncol. 2007; 29(1):1-17. PMC: 4618221. DOI: 10.1155/2007/586139. View

Meisner N, Hintersteiner M, Mueller K, Bauer R, Seifert J, Naegeli H . Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR. Nat Chem Biol. 2007; 3(8):508-15. DOI: 10.1038/nchembio.2007.14. View

Shao J, Sheng H, Inoue H, Morrow J, DuBois R . Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem. 2000; 275(43):33951-6. DOI: 10.1074/jbc.M002324200. View

Dixon D . Regulation of COX-2 expression in human cancers. Prog Exp Tumor Res. 2003; 37:52-71. DOI: 10.1159/000071363. View

Ming X, Stoecklin G, Lu M, Looser R, Moroni C . Parallel and independent regulation of interleukin-3 mRNA turnover by phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase. Mol Cell Biol. 2001; 21(17):5778-89. PMC: 87297. DOI: 10.1128/MCB.21.17.5778-5789.2001. View

Keene J . Why is Hu where? Shuttling of early-response-gene messenger RNA subsets. Proc Natl Acad Sci U S A. 1999; 96(1):5-7. PMC: 33538. DOI: 10.1073/pnas.96.1.5. View

Dean J, Sully G, Wait R, Rawlinson L, Clark A, Saklatvala J . Identification of a novel AU-rich-element-binding protein which is related to AUF1. Biochem J. 2002; 366(Pt 3):709-19. PMC: 1222842. DOI: 10.1042/BJ20020402. View

10.

Hall-Pogar T, Zhang H, Tian B, Lutz C . Alternative polyadenylation of cyclooxygenase-2. Nucleic Acids Res. 2005; 33(8):2565-79. PMC: 1088970. DOI: 10.1093/nar/gki544. View

11.

Dixon D, Kaplan C, McIntyre T, Zimmerman G, Prescott S . Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 3'-untranslated region. J Biol Chem. 2000; 275(16):11750-7. DOI: 10.1074/jbc.275.16.11750. View

12.

Cheadle C, Fan J, Cho-Chung Y, Werner T, Ray J, Do L . Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability. BMC Genomics. 2005; 6:75. PMC: 1156890. DOI: 10.1186/1471-2164-6-75. View

13.

Chakrabarty A, Tranguch S, Daikoku T, Jensen K, Furneaux H, Dey S . MicroRNA regulation of cyclooxygenase-2 during embryo implantation. Proc Natl Acad Sci U S A. 2007; 104(38):15144-9. PMC: 1986627. DOI: 10.1073/pnas.0705917104. View

14.

Chen C, Gherzi R, Ong S, Chan E, Raijmakers R, Pruijn G . AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell. 2001; 107(4):451-64. DOI: 10.1016/s0092-8674(01)00578-5. View

15.

Oshima M, Dinchuk J, Kargman S, Oshima H, Hancock B, Kwong E . Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell. 1996; 87(5):803-9. DOI: 10.1016/s0092-8674(00)81988-1. View

16.

Brennan C, Steitz J . HuR and mRNA stability. Cell Mol Life Sci. 2001; 58(2):266-77. PMC: 11146503. DOI: 10.1007/PL00000854. View

17.

Carballo E, Lai W, Blackshear P . Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science. 1998; 281(5379):1001-5. DOI: 10.1126/science.281.5379.1001. View

18.

Garneau N, Wilusz J, Wilusz C . The highways and byways of mRNA decay. Nat Rev Mol Cell Biol. 2007; 8(2):113-26. DOI: 10.1038/nrm2104. View

19.

Blanc V, Henderson J, Newberry R, Xie Y, Cho S, Newberry E . Deletion of the AU-rich RNA binding protein Apobec-1 reduces intestinal tumor burden in Apc(min) mice. Cancer Res. 2007; 67(18):8565-73. DOI: 10.1158/0008-5472.CAN-07-1593. View

20.

Dixon D, Tolley N, King P, Nabors L, McIntyre T, Zimmerman G . Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest. 2001; 108(11):1657-65. PMC: 200983. DOI: 10.1172/JCI12973. View