Nucleic Acids Research Advance Access published online on August 12, 2006
Nucleic Acids Research, doi:10.1093/nar/gkl571
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© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells
1 Experimental Pathology, Lund University Malmö, Sweden 2 Medical Microbiology at the Department of Laboratory Medicine, Malmö University Hospital, Lund University Malmö, Sweden
*To whom correspondence should be addressed at Experimental Pathology, Lund University, Malmö University Hospital, SE-205 02 Malmö, Sweden. Tel: +46 40 337768; Fax: +46 40 337353; Email: Karin.Leandersson{at}med.lu.se
Received April 27, 2006. Revised July 20, 2006. Accepted July 20, 2006.
Wnt-5a is a non-transforming Wnt protein. Since Wnt-5a mRNA and protein levels differ within and between tumours, the potential of Wnt-5a as a prognostic factor has been debated. We have previously shown that the lack of Wnt-5a protein is a predictor of shorter disease-free survival in human breast cancer. Recently, however, we also showed that the breast tumours lacking Wnt-5a protein had a high or normal level of Wnt-5a mRNA that might explain the discrepancies in previous studies. We here report that Wnt-5a is regulated at the post-transcriptional level. The regulation was mediated by the Embryonic Lethal Abnormal Vision (ELAV)-like protein HuR, which inhibited translation of Wnt-5a when bound to highly conserved AU-rich sequences in the 3'-untranslated region (3'-UTR) of the Wnt-5a mRNA molecule, as shown by both HA-tagged Wnt-5a- and Luciferase-Wnt-5a-3'-UTR reporter assays. The HuR-dependent inhibition of Wnt-5a was supported by the fact that active HuR is located in the cytoplasm in invasive human breast tumours and that hypoxia-induced activation of HuR inhibits translation of both Luciferase-Wnt-5a-3'-UTR and endogenous Wnt-5a protein. We propose that the lack of Wnt-5a protein expression in invasive human breast tumours is caused by a HuR-mediated suppression of Wnt-5a mRNA translation.
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