Cargando…

ADAR1-mediated RNA-editing of 3′UTRs in breast cancer

BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer...

Descripción completa

Detalles Bibliográficos
Autores principales: Sagredo, Eduardo A., Blanco, Alejandro, Sagredo, Alfredo I., Pérez, Paola, Sepúlveda-Hermosilla, Gonzalo, Morales, Fernanda, Müller, Bettina, Verdugo, Ricardo, Marcelain, Katherine, Harismendy, Olivier, Armisén, Ricardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172785/
https://www.ncbi.nlm.nih.gov/pubmed/30290838
http://dx.doi.org/10.1186/s40659-018-0185-4
_version_ 1783361010100338688
author Sagredo, Eduardo A.
Blanco, Alejandro
Sagredo, Alfredo I.
Pérez, Paola
Sepúlveda-Hermosilla, Gonzalo
Morales, Fernanda
Müller, Bettina
Verdugo, Ricardo
Marcelain, Katherine
Harismendy, Olivier
Armisén, Ricardo
author_facet Sagredo, Eduardo A.
Blanco, Alejandro
Sagredo, Alfredo I.
Pérez, Paola
Sepúlveda-Hermosilla, Gonzalo
Morales, Fernanda
Müller, Bettina
Verdugo, Ricardo
Marcelain, Katherine
Harismendy, Olivier
Armisén, Ricardo
author_sort Sagredo, Eduardo A.
collection PubMed
description BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. RESULTS: We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). CONCLUSIONS: Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6172785
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-61727852018-10-15 ADAR1-mediated RNA-editing of 3′UTRs in breast cancer Sagredo, Eduardo A. Blanco, Alejandro Sagredo, Alfredo I. Pérez, Paola Sepúlveda-Hermosilla, Gonzalo Morales, Fernanda Müller, Bettina Verdugo, Ricardo Marcelain, Katherine Harismendy, Olivier Armisén, Ricardo Biol Res Research Article BACKGROUND: Whole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed. RESULTS: We characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1). CONCLUSIONS: Altogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-05 /pmc/articles/PMC6172785/ /pubmed/30290838 http://dx.doi.org/10.1186/s40659-018-0185-4 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sagredo, Eduardo A.
Blanco, Alejandro
Sagredo, Alfredo I.
Pérez, Paola
Sepúlveda-Hermosilla, Gonzalo
Morales, Fernanda
Müller, Bettina
Verdugo, Ricardo
Marcelain, Katherine
Harismendy, Olivier
Armisén, Ricardo
ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title_full ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title_fullStr ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title_full_unstemmed ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title_short ADAR1-mediated RNA-editing of 3′UTRs in breast cancer
title_sort adar1-mediated rna-editing of 3′utrs in breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172785/
https://www.ncbi.nlm.nih.gov/pubmed/30290838
http://dx.doi.org/10.1186/s40659-018-0185-4
work_keys_str_mv AT sagredoeduardoa adar1mediatedrnaeditingof3utrsinbreastcancer
AT blancoalejandro adar1mediatedrnaeditingof3utrsinbreastcancer
AT sagredoalfredoi adar1mediatedrnaeditingof3utrsinbreastcancer
AT perezpaola adar1mediatedrnaeditingof3utrsinbreastcancer
AT sepulvedahermosillagonzalo adar1mediatedrnaeditingof3utrsinbreastcancer
AT moralesfernanda adar1mediatedrnaeditingof3utrsinbreastcancer
AT mullerbettina adar1mediatedrnaeditingof3utrsinbreastcancer
AT verdugoricardo adar1mediatedrnaeditingof3utrsinbreastcancer
AT marcelainkatherine adar1mediatedrnaeditingof3utrsinbreastcancer
AT harismendyolivier adar1mediatedrnaeditingof3utrsinbreastcancer
AT armisenricardo adar1mediatedrnaeditingof3utrsinbreastcancer