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The importance of enhancer methylation for epigenetic regulation of tumorigenesis in squamous lung cancer

Authors
 Jae-Won Cho  ;  Hyo Sup Shim  ;  Chang Young Lee  ;  Seong Yong Park  ;  Min Hee Hong  ;  Insuk Lee  ;  Hye Ryun Kim 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.54(1) : 12-22, 2022-01 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2022-01
MeSH
Carcinogenesis / genetics ; Carcinoma, Non-Small-Cell Lung* / genetics ; Carcinoma, Non-Small-Cell Lung* / pathology ; Carcinoma, Squamous Cell* / genetics ; Carcinoma, Squamous Cell* / pathology ; Cell Transformation, Neoplastic / genetics ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms* / genetics ; Lung Neoplasms* / pathology
Abstract
Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancer (NSCLC). LUSC occurs at the bronchi, shows a squamous appearance, and often occurs in smokers. To determine the epigenetic regulatory mechanisms of tumorigenesis, we performed a genome-wide analysis of DNA methylation in tumor and adjacent normal tissues from LUSC patients. With the Infinium Methylation EPIC Array, > 850,000 CpG sites, including ~350,000 CpG sites for enhancer regions, were profiled, and the differentially methylated regions (DMRs) overlapping promoters (pDMRs) and enhancers (eDMRs) between tumor and normal tissues were identified. Dimension reduction based on DMR profiles revealed that eDMRs alone and not pDMRs alone can differentiate tumors from normal tissues with the equivalent performance of total DMRs. We observed a stronger negative correlation of LUSC-specific gene expression with methylation for enhancers than promoters. Target genes of eDMRs rather than pDMRs were found to be enriched for tumor-associated genes and pathways. Furthermore, DMR methylation associated with immune infiltration was more frequently observed among enhancers than promoters. Our results suggest that methylation of enhancer regions rather than promoters play more important roles in epigenetic regulation of tumorigenesis and immune infiltration in LUSC.
Files in This Item:
T202204261.pdf Download
DOI
10.1038/s12276-021-00718-4
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Park, Seong Yong(박성용) ORCID logo https://orcid.org/0000-0002-5180-3853
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Chang Young(이창영)
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191182
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