华西口腔医学杂志2024,Vol.42Issue(3):319-328,10.DOI:10.7518/hxkq.2024.2023416
舌黏膜癌变基因组甲基化分析
Global analysis of DNA methylation changes during experimented lingual carcinogenesis
摘要
Abstract
Objective 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)tumorigen-esis,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,con-current with a decrease in promoter methylation levels in cell lines compared to normal mucosa.Conclusion DNA methylation changed during lingual carcinogenesis.Overexpression of SMAD1 was correlated to promoter hypomethyl-ation in tongue cancer cell lines.关键词
舌癌/发病机制/甲基化/动物模型/甲基化DNA免疫沉淀测序/差异表达基因Key words
tongue cancer/pathogenesis/methylation/animal model/methylated DNA immunoprecipitation sequencing/differentially expressed genes分类
医药卫生引用本文复制引用
刘华,岳万远,邵帅,孙家平,杨莹,代晓明..舌黏膜癌变基因组甲基化分析[J].华西口腔医学杂志,2024,42(3):319-328,10.基金项目
Joint Special Project of KUM by Yunnan Provincial Science and Technology Department[202001AY07-0001-253,2018FE001(-216)]云南省科技厅-昆医联合专项[202001AY070001-253,2018FE001(-216)] (-216)