Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers
DNA methylation dysregulation during carcinogenesis has been widely discussed in recent years. However, the pan-cancer DNA methylation biomarkers and corresponding biological mechanisms were seldom investigated. We identified differentially methylated sites and regions from 5,056 The Cancer Genome A...
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doaj-6b85444521aa40368927c593f5e090a72021-03-18T08:34:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.649168649168Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of CancersGang Liu0Zhenhao Liu1Zhenhao Liu2Xiaomeng Sun3Xiaoqiong Xia4Yunhe Liu5Lei Liu6Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaKey Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Key Laboratory of Carcinogenesis, National Health and Family Planning Commission, Xiangya Hospital, Central South University, Changsha, ChinaShanghai Center for Bioinformation Technology, Shanghai, ChinaInstitute of Biomedical Sciences, Fudan University, Shanghai, ChinaInstitute of Biomedical Sciences, Fudan University, Shanghai, ChinaInstitute of Biomedical Sciences, Fudan University, Shanghai, ChinaInstitute of Biomedical Sciences, Fudan University, Shanghai, ChinaDNA methylation dysregulation during carcinogenesis has been widely discussed in recent years. However, the pan-cancer DNA methylation biomarkers and corresponding biological mechanisms were seldom investigated. We identified differentially methylated sites and regions from 5,056 The Cancer Genome Atlas (TCGA) samples across 10 cancer types and then validated the findings using 48 manually annotated datasets consisting of 3,394 samples across nine cancer types from Gene Expression Omnibus (GEO). All samples’ DNA methylation profile was evaluated with Illumina 450K microarray to narrow down the batch effect. Nine regions were identified as commonly differentially methylated regions across cancers in TCGA and GEO cohorts. Among these regions, a DNA fragment consisting of ∼1,400 bp detected inside the HOXA locus instead of the boundary may relate to the co-expression attenuation of genes inside the locus during carcinogenesis. We further analyzed the 3D DNA interaction profile by the publicly accessible Hi-C database. Consistently, the HOXA locus in normal cell lines compromised isolated topological domains while merging to the domain nearby in cancer cell lines. In conclusion, the dysregulation of the HOXA locus provides a novel insight into pan-cancer carcinogenesis.https://www.frontiersin.org/articles/10.3389/fcell.2021.649168/fullpan-cancerDNA methylationbiomarkerHi-Choxcarcinogenesis |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gang Liu Zhenhao Liu Zhenhao Liu Xiaomeng Sun Xiaoqiong Xia Yunhe Liu Lei Liu |
spellingShingle |
Gang Liu Zhenhao Liu Zhenhao Liu Xiaomeng Sun Xiaoqiong Xia Yunhe Liu Lei Liu Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers Frontiers in Cell and Developmental Biology pan-cancer DNA methylation biomarker Hi-C hox carcinogenesis |
author_facet |
Gang Liu Zhenhao Liu Zhenhao Liu Xiaomeng Sun Xiaoqiong Xia Yunhe Liu Lei Liu |
author_sort |
Gang Liu |
title |
Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers |
title_short |
Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers |
title_full |
Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers |
title_fullStr |
Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers |
title_full_unstemmed |
Pan-Cancer Genome-Wide DNA Methylation Analyses Revealed That Hypermethylation Influences 3D Architecture and Gene Expression Dysregulation in HOXA Locus During Carcinogenesis of Cancers |
title_sort |
pan-cancer genome-wide dna methylation analyses revealed that hypermethylation influences 3d architecture and gene expression dysregulation in hoxa locus during carcinogenesis of cancers |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-03-01 |
description |
DNA methylation dysregulation during carcinogenesis has been widely discussed in recent years. However, the pan-cancer DNA methylation biomarkers and corresponding biological mechanisms were seldom investigated. We identified differentially methylated sites and regions from 5,056 The Cancer Genome Atlas (TCGA) samples across 10 cancer types and then validated the findings using 48 manually annotated datasets consisting of 3,394 samples across nine cancer types from Gene Expression Omnibus (GEO). All samples’ DNA methylation profile was evaluated with Illumina 450K microarray to narrow down the batch effect. Nine regions were identified as commonly differentially methylated regions across cancers in TCGA and GEO cohorts. Among these regions, a DNA fragment consisting of ∼1,400 bp detected inside the HOXA locus instead of the boundary may relate to the co-expression attenuation of genes inside the locus during carcinogenesis. We further analyzed the 3D DNA interaction profile by the publicly accessible Hi-C database. Consistently, the HOXA locus in normal cell lines compromised isolated topological domains while merging to the domain nearby in cancer cell lines. In conclusion, the dysregulation of the HOXA locus provides a novel insight into pan-cancer carcinogenesis. |
topic |
pan-cancer DNA methylation biomarker Hi-C hox carcinogenesis |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.649168/full |
work_keys_str_mv |
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