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Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets
A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758889/ https://www.ncbi.nlm.nih.gov/pubmed/29165639 http://dx.doi.org/10.1093/nar/gkx1176 |
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author | Pinto, Yishay Buchumenski, Ilana Levanon, Erez Y Eisenberg, Eli |
author_facet | Pinto, Yishay Buchumenski, Ilana Levanon, Erez Y Eisenberg, Eli |
author_sort | Pinto, Yishay |
collection | PubMed |
description | A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications. |
format | Online Article Text |
id | pubmed-5758889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57588892018-01-16 Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets Pinto, Yishay Buchumenski, Ilana Levanon, Erez Y Eisenberg, Eli Nucleic Acids Res Computational Biology A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications. Oxford University Press 2018-01-09 2017-11-20 /pmc/articles/PMC5758889/ /pubmed/29165639 http://dx.doi.org/10.1093/nar/gkx1176 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Computational Biology Pinto, Yishay Buchumenski, Ilana Levanon, Erez Y Eisenberg, Eli Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title | Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title_full | Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title_fullStr | Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title_full_unstemmed | Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title_short | Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets |
title_sort | human cancer tissues exhibit reduced a-to-i editing of mirnas coupled with elevated editing of their targets |
topic | Computational Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758889/ https://www.ncbi.nlm.nih.gov/pubmed/29165639 http://dx.doi.org/10.1093/nar/gkx1176 |
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