Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells.
Leandersson, Karin LU
; Riesbeck, Kristian
LU
and Andersson, Tommy
LU
(2006)
In Nucleic Acids Research
34(14).
p.3988-3999
- Abstract
- 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... (More)
- 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-Wnt5a-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.. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/160073
- author
- Leandersson, Karin
LU
; Riesbeck, Kristian
LU
and Andersson, Tommy
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nucleic Acids Research
- volume
- 34
- issue
- 14
- pages
- 3988 - 3999
- publisher
- Oxford University Press
- external identifiers
-
- pmid:16914445
- wos:000240583800020
- scopus:33748575589
- ISSN
- 1362-4962
- DOI
- 10.1093/nar/gkl571
- language
- English
- LU publication?
- yes
- id
- 5b729559-2c22-4c4d-9077-699a3da2a886 (old id 160073)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16914445&dopt=Abstract
- date added to LUP
- 2016-04-01 12:21:53
- date last changed
- 2022-11-10 02:09:37
@article{5b729559-2c22-4c4d-9077-699a3da2a886,
abstract = {{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-Wnt5a-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..}},
author = {{Leandersson, Karin and Riesbeck, Kristian and Andersson, Tommy}},
issn = {{1362-4962}},
language = {{eng}},
number = {{14}},
pages = {{3988--3999}},
publisher = {{Oxford University Press}},
series = {{Nucleic Acids Research}},
title = {{Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells.}},
url = {{http://dx.doi.org/10.1093/nar/gkl571}},
doi = {{10.1093/nar/gkl571}},
volume = {{34}},
year = {{2006}},
}