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β-Catenin stabilizes Cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3′-UTR

By Hee Kyu Lee and Sunjoo Jeong


Cyclooxygenase-2 (COX-2) mRNA is induced in the majority of human colorectal carcinomas. Transcriptional regulation plays a key role in COX-2 expression in human colon carcinoma cells, but post-transcriptional regulation of its mRNA is also critical for tumorigenesis. Expression of COX-2 mRNA is regulated by various cytokines, growth factors and other signals. β-Catenin, a key transcription factor in the Wnt signal pathway, activates transcription of COX-2. Here we found that COX-2 mRNA was also substantially stabilized by activating β-catenin in NIH3T3 and 293T cells. We identified the β-catenin-responsive element in the proximal region of the COX-2 3′-untranslated region (3′-UTR) and showed that β-catenin interacted with AU-rich elements (ARE) of 3′-UTR in vitro and in vivo. Interestingly, β-catenin induced the cytoplasmic localization of the RNA stabilizing factor, HuR, which may bind to β-catenin in an RNA-mediated complex and facilitate β-catenin-dependent stabilization of COX-2 mRNA. Taken together, we provided evidences for β-catenin as an RNA-binding factor and a regulator of stabilization of COX-2 mRNA

Topics: RNA
Publisher: Oxford University Press
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Provided by: PubMed Central
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    1. (2002). A unified theory of gene expression.
    2. (2001). Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells.
    3. (2002). An extensive network of coupling among gene expression machines.
    4. (1998). An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of b-catenin.
    5. (2001). AU binding proteins recruit the exosome to degrade ARE-containing mRNAs.
    6. (2006). AU-rich elements and associated factors: are there unifying principles?
    7. (1995). AU-rich elements: characterization and importance in mRNA degradation.
    8. (2005). b-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing.
    9. (2003). b-catenin inversely regulates vascular endothelial growth factor-D mRNA stability.
    10. (1999). b-Catenin regulates expression of cyclin D1 in colon carcinoma cells.
    11. (2001). Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2.
    12. (2004). Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.
    13. (2001). Cyclooxygenase-2: a novel target for cancer chemotherapy?
    14. (1998). Downregulation of b-catenin by human Axin and its association with the APC tumor suppressor, b-catenin and GSK3b.
    15. (1996). Functional characterization of a non-AUUUA AU-rich element from the c-jun proto-oncogene mRNA: evidence for a novel class of AU-rich elements.
    16. (2002). Having it both ways: transcription factors that bind DNA and RNA.
    17. (2000). HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation.
    18. (2001). Identification of an RNA binding specificity for the potential splicing factor TLS.
    19. (1998). Identification of c-myc as a target of the APC pathway.
    20. (2004). Identification of RNA-binding proteins in RAW 264.7 cells that recognize a lipopolysaccharide-responsive element in the 30-untranslated region of the murine cyclooxygenase-2 mRNA.
    21. (2005). Inhibition of the DNA binding by the TCF-1 binding RNA aptamer.
    22. (2004). Inhibition of the functions of the nucleocapsid protein of human immunodeficiency virus-1 by an RNA aptamer.
    23. (1999). Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level.
    24. (2005). Involvement of microRNA in AU-rich element-mediated mRNA instability.
    25. (2001). New aspects of Wnt signaling pathways in higher vertebrates.
    26. (2000). Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.
    27. (2002). Oncogenic b-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer.
    28. (2000). Post-transcriptional control of cyclooxygenase-2 gene expression. The role of the 30-untranslated region.
    29. (2000). Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial cells.
    30. (2003). Regulation of cyclooxygenase-2 expression by the Wnt and ras pathways.
    31. (2002). Reversible cross-linking combined with immunoprecipitation to study RNA–protein interactions in vivo.
    32. (2003). Role of the RNA-binding protein HuR in colon carcinogenesis.
    33. (1997). Stabilization of b-catenin by genetic defects in melanoma cell lines.
    34. (2002). The b-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
    35. (2003). The proximal region of the 30-untranslated region of cyclooxygenase-2 is recognized by a multimeric protein complex containing HuR, TIA-1, TIAR, and the heterogeneous nuclear ribonucleoprotein U.
    36. (2003). The RNA-binding protein HuR regulates the expression of cyclooxygenase-2.
    37. (2003). The Wnt/b-catenin!Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs.
    38. (1999). Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells.
    39. (1999). Transcriptional pulsing approaches for analysis of mRNA turnover in mammalian cells.
    40. (2000). Wnt signaling and cancer.
    41. (2005). Wnt signaling in the intestinal epithelium: from endoderm to cancer.
    42. (1997). Wnt signaling: a common theme in animal development.
    43. (2006). Wnt signaling: is the party in the nucleus?

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