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Updated: Jun 19, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Global analysis of DNA methylation changes during experimented lingual carcinogenesis
Hua Liu1, Wanyuan Yue1, Shuai Shao1
1Dept. of Oral and Maxillofacial Surgery, Affiliated Hospital of Yunnan University, Kunming 650021, China.
Objectives:
This study aims to assess the role of DNA methylation changes in tongue cancer through a comprehensive analysis of global DNA methylation alterations during experimental lingual carcinogenesis.
Methods:
C57BL/6J mice were subjected to 16-week oral administration of 4-nitroquinoline-1-oxide (4NQO, 50 mg/L). Lingual mucosa samples, being representative of normal tissue (week 0) and early (week 12) and advanced (week 28) tumorigenesis, were harvested for microarray and methylated DNA immunoprecipitation sequencing (MeDIP-Seq). The mRNA and promoter methylation of transforming growth factor-beta-signaling protein 1 (SMAD1) were evaluated with real-time quantitative reverse transcription polymerase chain reaction and Massarray in human lingual mucosa and tongue cancer cell lines.
Results:
The cytosine guanine island (CGI) methylation level observed at 28 weeks surpassed that of both 12 weeks and 0 weeks. The promoter methylation level at 12 weeks exceeded that at 0 weeks. Notably, 208 differentially expressed genes were negatively correlated to differential methylation in promoters among 0, 12, and 28 weeks. The mRNA of SMAD1 was upregulated, concurrent with a decrease in promoter methylation levels in cell lines compared to normal mucosa.
Conclusions:
DNA methylation changed during lingual carcinogenesis. Overexpression of SMAD1 was correlated to promoter hypomethylation in tongue cancer cell lines.
