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Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer

Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput s...

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Autores principales: Li, Xiaoyan, Liu, Yining, Lu, Jiachun, Zhao, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710946/
https://www.ncbi.nlm.nih.gov/pubmed/29207666
http://dx.doi.org/10.18632/oncotarget.21227
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author Li, Xiaoyan
Liu, Yining
Lu, Jiachun
Zhao, Min
author_facet Li, Xiaoyan
Liu, Yining
Lu, Jiachun
Zhao, Min
author_sort Li, Xiaoyan
collection PubMed
description Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput sequencing. Enhancers have been associated with malfunctions in cancer development resulting from point mutations in regulatory regions. However, the potential impact of copy number variations (CNVs) on enhancer regions is unknown. To learn more about the relationship between enhancers and cancer, we integrated the CNVs data on enhancers and explored their targeting gene expression pattern in high-grade ovarian cancer. Using human enhancer-gene interaction data with 13,691 interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found that the 2,910 copy number gain events of enhancer are significantly correlated with the up-regulation of targeting genes. We further identified that a number of highly mutated super-enhancers, with concordant gene expression change on their targeting genes. We also identified 18 targeting genes by super-enhancers with prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B. We are the first to report that abundant copy number variations on enhancers could change the expression of their targeting genes which would be valuable for the design of enhancer-based cancer treatment strategy.
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spelling pubmed-57109462017-12-04 Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer Li, Xiaoyan Liu, Yining Lu, Jiachun Zhao, Min Oncotarget Research Paper Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput sequencing. Enhancers have been associated with malfunctions in cancer development resulting from point mutations in regulatory regions. However, the potential impact of copy number variations (CNVs) on enhancer regions is unknown. To learn more about the relationship between enhancers and cancer, we integrated the CNVs data on enhancers and explored their targeting gene expression pattern in high-grade ovarian cancer. Using human enhancer-gene interaction data with 13,691 interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found that the 2,910 copy number gain events of enhancer are significantly correlated with the up-regulation of targeting genes. We further identified that a number of highly mutated super-enhancers, with concordant gene expression change on their targeting genes. We also identified 18 targeting genes by super-enhancers with prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B. We are the first to report that abundant copy number variations on enhancers could change the expression of their targeting genes which would be valuable for the design of enhancer-based cancer treatment strategy. Impact Journals LLC 2017-09-23 /pmc/articles/PMC5710946/ /pubmed/29207666 http://dx.doi.org/10.18632/oncotarget.21227 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Xiaoyan
Liu, Yining
Lu, Jiachun
Zhao, Min
Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title_full Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title_fullStr Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title_full_unstemmed Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title_short Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
title_sort integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710946/
https://www.ncbi.nlm.nih.gov/pubmed/29207666
http://dx.doi.org/10.18632/oncotarget.21227
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