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The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma

Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implicated in cancer development and response to different ther...

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Autores principales: Sanlorenzo, Martina, Vujic, Igor, Esteve-Puig, Rosaura, Lai, Kevin, Vujic, Marin, Lin, Kevin, Posch, Christian, Dimon, Michelle, Moy, Adrian, Zekhtser, Mitchell, Johnston, Katia, Gho, Deborah, Ho, Wilson, Gajjala, Abhinay, Oses Prieto, Juan, Burlingame, Alma, Daud, Adil, Rappersberger, Klemens, Ortiz-Urda, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053443/
https://www.ncbi.nlm.nih.gov/pubmed/30026510
http://dx.doi.org/10.1038/s41598-018-27643-3
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author Sanlorenzo, Martina
Vujic, Igor
Esteve-Puig, Rosaura
Lai, Kevin
Vujic, Marin
Lin, Kevin
Posch, Christian
Dimon, Michelle
Moy, Adrian
Zekhtser, Mitchell
Johnston, Katia
Gho, Deborah
Ho, Wilson
Gajjala, Abhinay
Oses Prieto, Juan
Burlingame, Alma
Daud, Adil
Rappersberger, Klemens
Ortiz-Urda, Susana
author_facet Sanlorenzo, Martina
Vujic, Igor
Esteve-Puig, Rosaura
Lai, Kevin
Vujic, Marin
Lin, Kevin
Posch, Christian
Dimon, Michelle
Moy, Adrian
Zekhtser, Mitchell
Johnston, Katia
Gho, Deborah
Ho, Wilson
Gajjala, Abhinay
Oses Prieto, Juan
Burlingame, Alma
Daud, Adil
Rappersberger, Klemens
Ortiz-Urda, Susana
author_sort Sanlorenzo, Martina
collection PubMed
description Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implicated in cancer development and response to different therapeutics and are thus potential treatment targets; however, the majority of their functions and molecular interactions remain unexplored. In this study, we identify a novel cytoplasmic intergenic lincRNA (MIRAT), which is upregulated following prolonged MAPK inhibition in NRAS mutant melanoma and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1. Collectively, our results present MIRAT’s direct modulatory effect on the MAPK pathway and highlight the relevance of cytoplasmic lncRNAs as potential targets in drug resistant cancer.
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spelling pubmed-60534432018-07-23 The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma Sanlorenzo, Martina Vujic, Igor Esteve-Puig, Rosaura Lai, Kevin Vujic, Marin Lin, Kevin Posch, Christian Dimon, Michelle Moy, Adrian Zekhtser, Mitchell Johnston, Katia Gho, Deborah Ho, Wilson Gajjala, Abhinay Oses Prieto, Juan Burlingame, Alma Daud, Adil Rappersberger, Klemens Ortiz-Urda, Susana Sci Rep Article Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implicated in cancer development and response to different therapeutics and are thus potential treatment targets; however, the majority of their functions and molecular interactions remain unexplored. In this study, we identify a novel cytoplasmic intergenic lincRNA (MIRAT), which is upregulated following prolonged MAPK inhibition in NRAS mutant melanoma and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1. Collectively, our results present MIRAT’s direct modulatory effect on the MAPK pathway and highlight the relevance of cytoplasmic lncRNAs as potential targets in drug resistant cancer. Nature Publishing Group UK 2018-07-19 /pmc/articles/PMC6053443/ /pubmed/30026510 http://dx.doi.org/10.1038/s41598-018-27643-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sanlorenzo, Martina
Vujic, Igor
Esteve-Puig, Rosaura
Lai, Kevin
Vujic, Marin
Lin, Kevin
Posch, Christian
Dimon, Michelle
Moy, Adrian
Zekhtser, Mitchell
Johnston, Katia
Gho, Deborah
Ho, Wilson
Gajjala, Abhinay
Oses Prieto, Juan
Burlingame, Alma
Daud, Adil
Rappersberger, Klemens
Ortiz-Urda, Susana
The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title_full The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title_fullStr The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title_full_unstemmed The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title_short The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma
title_sort lincrna mirat binds to iqgap1 and modulates the mapk pathway in nras mutant melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053443/
https://www.ncbi.nlm.nih.gov/pubmed/30026510
http://dx.doi.org/10.1038/s41598-018-27643-3
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