Gastroenterology
Volume 136, Issue 5 , Pages 1669-1679 , May 2009

The mRNA Binding Proteins HuR and Tristetraprolin Regulate Cyclooxygenase 2 Expression During Colon Carcinogenesis

  • Lisa E. Young

      Affiliations

    • Department of Biological Sciences and Cancer Research Center, University of South Carolina, Columbia, South Carolina
    • ,
  • Sandhya Sanduja

      Affiliations

    • Department of Biological Sciences and Cancer Research Center, University of South Carolina, Columbia, South Carolina
    • ,
  • Kristi Bemis–Standoli

      Affiliations

    • Department of Biological Sciences and Cancer Research Center, University of South Carolina, Columbia, South Carolina
    • ,
  • Edsel A. Pena

      Affiliations

    • Department of Statistics, University of South Carolina, Columbia, South Carolina
    • ,
  • Robert L. Price

      Affiliations

    • Department of Cell and Developmental Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina
    • ,
  • Dan A. Dixon

      Affiliations

    • Department of Biological Sciences and Cancer Research Center, University of South Carolina, Columbia, South Carolina
    • Corresponding Author InformationReprint requests Address requests for reprints to: Dan A. Dixon, PhD, Cancer Research Center, University of South Carolina, 14 Medical Park Drive, Suite 500, Columbia, South Carolina, 29203. fax: (803) 434-3795

Received 31 July 2008 ,Accepted 9 January 2009.

References 

  1. Garneau NL, Wilusz J, Wilusz CJ. The highways and byways of mRNA decay. Nat Rev Mol Cell Biol. 2007;8:113–126
  2. Dixon DA, Tolley ND, King PH, et al. Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. J Clin Invest. 2001;108:1657–1665
  3. Lopez de Silanes I, Fan J, Yang X, et al. Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene. 2003;22:7146–7154
  4. Benjamin D, Moroni C. mRNA stability and cancer: an emerging link?. Expert Opin Biol Ther. 2007;7:1515–1529
  5. Fan XC, Steitz JA. Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J. 1998;17:3448–3460
  6. Lai WS, Carballo E, Thorn JM, et al. Interactions of CCCH zinc finger proteins with mRNA (Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA). J Biol Chem. 2000;275:17827–17837
  7. Hau HH, Walsh RJ, Ogilvie RL, et al. Tristetraprolin recruits functional mRNA decay complexes to ARE sequences. J Cell Biochem. 2007;100:1477–1492
  8. Wang D, Mann JR, DuBois RN. The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology. 2005;128:1445–1461
  9. Dixon DA, Kaplan CD, McIntyre TM, et al. Posttranscriptional control of cyclooxygenase-2 gene expression (The role of the 3′-untranslated region). J Biol Chem. 2000;275:11750–11757
  10. Dixon DA. Regulation of COX-2 expression in human cancer. Prog Exp Tumor Res. 2003;37:52–71
  11. Denkert C, Koch I, von Keyserlingk N, et al. Expression of the ELAV-like protein HuR in human colon cancer: association with tumor stage and cyclooxygenase-2. Mod Pathol. 2006;9:1261–1269
  12. Sawaoka H, Dixon DA, Oates JA, et al. Tristetrapolin binds to the 3′ untranslated region of cyclooxygenase-2 mRNA: a polyadenylation variant in a cancer cell line lacks the binding site. J Biol Chem. 2003;278:13928–13935
  13. Williams CS, Watson AJ, Sheng H, et al. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res. 2000;60:6045–6051
  14. Eberhart CE, Coffey RJ, Radhika A, et al. Up-regulation of cycloxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107:1183–1188
  15. Shao J, Sheng H, Inoue H, et al. Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem. 2000;43:33951–33956
  16. Kargman S, O'Neill G, Vickers P, et al. Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res. 1995;55:2556–2559
  17. Zhang H, Sun XF. Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer. Am J Gastroenterol. 2002;97:1037–1041
  18. Hasegawa K, Ichikawa W, Fujita T, et al. Expression of cycloOxygenase-2 (COX-2) mRNA in human colorectal adenomas. Eur J Cancer. 2001;37:1469–1474
  19. Einspahr JG, Krouse RS, Yochim JM, et al. Association between cyclooxygenase expression and colorectal adenoma characteristics. Cancer Res. 2003;63:3891–3893
  20. Heinonen M, Bono P, Narko K, et al. Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma. Cancer Res. 2005;65:2157–2161
  21. Erkinheimo TL, Lassus H, Sivula A, et al. Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma. Cancer Res. 2003;63:7591–7594
  22. Mrena J, Wiksten JP, Thiel A, et al. Cyclooxygenase-2 is an independent prognostic factor in gastric cancer and its expression is regulated by the messenger RNA stability factor HuR. Clin Cancer Res. 2005;11:7362–7368
  23. Levadoux-Martin M, Gouble A, Jégou B, et al. Impaired gametogenesis in mice that overexpress the RNA-binding protein HuR. EMBO Rep. 2003;4:394–399
  24. Katsanou V, Papadaki O, Milatos S, et al. HuR as a negative posttranscriptional modulator in inflammation. Mol Cell. 2005;19:777–789
  25. Phillips K, Kedersha N, Shen L, et al. Arthritis suppressor genes TIA-1 and TTP dampen the expression of tumor necrosis factor α, cyclooxygenase 2, and inflammatory arthritis. Proc Natl Acad Sci U S A. 2004;101:2011–2016
  26. Stoecklin G, Gross B, Ming XF, et al. A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA. Oncogene. 2003;22:3554–3561
  27. Carrick DM, Blackshear PJ. Comparative expression of tristetraprolin (TTP) family member transcripts in normal human tissues and cancer cell lines. Arch Biochem Biophys. 2007;462:278–285
  28. Staub E, Grone J, Mennerich D, et al. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer. Mol Cancer. 2006;5:37
  29. Kang MJ, Ryu BK, Lee MG, et al. NF-κB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology. 2008;135:2030–2042
  30. King PH, Fuller JJ, Nabors LB, et al. Analysis of the 5′ end of the mouse Elavl1 (mHuA) gene reveals a transcriptional regulatory element and evidence for conserved genomic organization. Gene. 2000;242:125–131
  31. Tchen CR, Brook M, Saklatvala J, et al. The stability of tristetraprolin mRNA is regulated by mitogen-activated protein kinase p38 and by tristetraprolin itself. J Biol Chem. 2004;279:32393–32400
  32. Bakheet T, Williams BR, Khabar KS. ARED 3.0: the large and diverse AU-rich transcriptome. Nucleic Acids Res. 2006;34:D111–D114
  33. Kanies CL, Smith JJ, Kis C, et al. Oncogenic Ras and transforming growth factor-β synergistically regulate AU-rich element-containing mRNAs during epithelial to mesenchymal transition. Mol Cancer Res. 2008;6:1124–1136

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by grants P20 RR017698 from the National Institutes of Health, and RSG-06-122-01-CNE from the American Cancer Society (to D.A.D.).

PII: S0016-5085(09)00040-7

doi: 10.1053/j.gastro.2009.01.010

Gastroenterology
Volume 136, Issue 5 , Pages 1669-1679 , May 2009

Article Tools

* Image Usage & Resolution