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LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression
RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is co...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430325/ https://www.ncbi.nlm.nih.gov/pubmed/25531318 http://dx.doi.org/10.1038/onc.2014.428 |
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author | Mura, M Hopkins, T G Michael, T Abd-Latip, N Weir, J Aboagye, E Mauri, F Jameson, C Sturge, J Gabra, H Bushell, M Willis, A E Curry, E Blagden, S P |
author_facet | Mura, M Hopkins, T G Michael, T Abd-Latip, N Weir, J Aboagye, E Mauri, F Jameson, C Sturge, J Gabra, H Bushell, M Willis, A E Curry, E Blagden, S P |
author_sort | Mura, M |
collection | PubMed |
description | RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression. |
format | Online Article Text |
id | pubmed-4430325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44303252016-01-07 LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression Mura, M Hopkins, T G Michael, T Abd-Latip, N Weir, J Aboagye, E Mauri, F Jameson, C Sturge, J Gabra, H Bushell, M Willis, A E Curry, E Blagden, S P Oncogene Original Article RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5′-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression. Nature Publishing Group 2015-09-24 2014-12-22 /pmc/articles/PMC4430325/ /pubmed/25531318 http://dx.doi.org/10.1038/onc.2014.428 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Mura, M Hopkins, T G Michael, T Abd-Latip, N Weir, J Aboagye, E Mauri, F Jameson, C Sturge, J Gabra, H Bushell, M Willis, A E Curry, E Blagden, S P LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title | LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title_full | LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title_fullStr | LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title_full_unstemmed | LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title_short | LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression |
title_sort | larp1 post-transcriptionally regulates mtor and contributes to cancer progression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430325/ https://www.ncbi.nlm.nih.gov/pubmed/25531318 http://dx.doi.org/10.1038/onc.2014.428 |
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