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The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly describ...

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Autores principales: Zhao, Xiaoxiao, Ji, Jianghuai, Wang, Shijia, Wang, Rendong, Yu, Qiuhong, Li, Dongguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420065/
https://www.ncbi.nlm.nih.gov/pubmed/34482818
http://dx.doi.org/10.1186/s12859-021-04345-8
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author Zhao, Xiaoxiao
Ji, Jianghuai
Wang, Shijia
Wang, Rendong
Yu, Qiuhong
Li, Dongguo
author_facet Zhao, Xiaoxiao
Ji, Jianghuai
Wang, Shijia
Wang, Rendong
Yu, Qiuhong
Li, Dongguo
author_sort Zhao, Xiaoxiao
collection PubMed
description BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described. RESULTS: We integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment. CONCLUSIONS: Our study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04345-8.
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spelling pubmed-84200652021-09-09 The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma Zhao, Xiaoxiao Ji, Jianghuai Wang, Shijia Wang, Rendong Yu, Qiuhong Li, Dongguo BMC Bioinformatics Research BACKGROUND: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described. RESULTS: We integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment. CONCLUSIONS: Our study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04345-8. BioMed Central 2021-09-05 /pmc/articles/PMC8420065/ /pubmed/34482818 http://dx.doi.org/10.1186/s12859-021-04345-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhao, Xiaoxiao
Ji, Jianghuai
Wang, Shijia
Wang, Rendong
Yu, Qiuhong
Li, Dongguo
The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title_full The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title_fullStr The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title_full_unstemmed The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title_short The regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
title_sort regulatory pattern of target gene expression by aberrant enhancer methylation in glioblastoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420065/
https://www.ncbi.nlm.nih.gov/pubmed/34482818
http://dx.doi.org/10.1186/s12859-021-04345-8
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