Genome-wide profiling of DNA methylation and gene expression in esophageal squamous cell carcinoma
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Chen Chen1, Hao Peng2, Xiaojie Huang3, Ming Zhao4, Zhi Li5, Ni Yin3, Xiang Wang1, Fenglei Yu1, Bangliang Yin1, Yunchang Yuan1, Qianjin Lu4
1Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, P.R. China
2Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, P.R. China
3Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, P.R. China
4Hunan Key Laboratory of Medical Epigenomics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, P.R. China
5Beijing Genomics Institute at Shenzhen, Shenzhen, P.R. China
Yunchang Yuan, e-mail: [email protected]
Qianjin Lu, e-mail: [email protected]
Keywords: esophageal squamous cell carcinoma, MeDIP-Seq, DNA methylation, RNA-Seq, gene expression
Received: September 07, 2015 Accepted: November 26, 2015 Published: December 14, 2015
Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide. Previous studies have suggested that DNA methylation involved in the development of ESCC. However, the precise mechanisms underlying the regulation and maintenance of the methylome as well as their relationship with ESCC remain poorly understood. Herein, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) and RNA-Seq to investigate whole-genome DNA methylation patterns and the genome expression profiles in ESCC samples. The results of MeDIP-Seq analyses identified differentially methylated regions (DMRs) covering almost the entire genome with sufficient depth and high resolution. The gene ontology (GO) analysis showed that the DMRs related genes belonged to several different ontological domains, such as cell cycle, adhesion, proliferation and apoptosis. The RNA-Seq analysis identified a total of 6150 differentially expressed genes (3423 up-regulated and 2727 down-regulated). The significant GO terms showed that these genes belonged to several molecular functions and biological pathways. Moreover, the bisulfite-sequencing of genes MLH1, CDH5, TWIST1 and CDX1 confirmed the methylation status identified by MeDIP-Seq. And the mRNA expression levels of MLH1, TWIST1 and CDX1 were consistent with their DNA methylation profiles. The DMR region of MLH1 was found to correlate with survival. The identification of whole-genome DNA methylation patterns and gene expression profiles in ESCC provides new insight into the carcinogenesis of ESCC and represents a promising avenue through which to investigate novel therapeutic targets.
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