The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells
Open accessAbstract
Cyclooxygenase-2 (COX-2) expression is normally tightly regulated. However, constitutive overexpression plays a key role in colon carcinogenesis. To understand the molecular nature of enhanced COX-2 expression detected in colon cancer, we examined the ability of the AU-rich element-containing (ARE-containing) 3' untranslated region (3'UTR) of COX-2 mRNA to regulate rapid mRNA decay in human colon cancer cells. In tumor cells displaying enhanced growth and tumorigenicity that is correlated with elevated COX-2, vascular endothelial growth factor (VEGF), and IL-8 protein levels, the corresponding mRNAs were transcribed constitutively and turned over slowly. The observed mRNA stabilization is owing to defective recognition of class II-type AREs present within the COX-2, VEGF, and IL-8 3'UTRs; c-myc mRNA, containing a class I ARE decayed rapidly in the same cells. Correlating with cellular defects in mRNA stability, the RNA-binding of trans-acting cellular factors was altered. In particular, we found that the RNA-stability factor HuR binds to the COX-2 ARE, and overexpression of HuR, as detected in tumors, results in elevated expression of COX-2, VEGF, and IL-8. These findings demonstrate the functional significance rapid mRNA decay plays in controlling gene expression and show that dysregulation of these trans-acting factors can lead to overexpression of COX-2 and other angiogenic proteins, as detected in neoplasia.
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Cites
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Cited by
AU-rich elements and associated factors: are there unifying principles?
Barreau, C. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki1012 · Cited by 907
New frontiers in translational control of the cancer genome
Truitt, M. L., & Ruggero, D. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.27 · Cited by 378
Srikantan, S. (2012) · Frontiers in Bioscience · doi:10.2741/3921 · Cited by 353
ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5′UTR
Kullmann, M., Göpfert, U., Siewe, B., & Hengst, L. (2002) · Genes & Development · doi:10.1101/gad.248902 · Cited by 327
UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression
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Metadata
- Authors
- Dixon, D. A., Tolley, N. D., King, P. H., Nabors, L. B., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-12-01
- Volume
- 108
- Issue
- 11
- Pages
- 1657-1665
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2014209078
- Cited by
- 444
- References
- 46
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dixon, D. A., Tolley, N. D., King, P. H., Nabors, L. B., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M. (2001). Altered expression of the mRNA stability factor HuR promotes cyclooxygenase-2 expression in colon cancer cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci12973
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