{Reference Type}: Journal Article
{Title}: Global analysis of DNA methylation changes during experimented lingual carcinogenesis.
{Author}: Liu H;Yue W;Shao S;Sun J;Yang Y;Dai X;
{Journal}: Hua Xi Kou Qiang Yi Xue Za Zhi
{Volume}: 42
{Issue}: 3
{Year}: 2024 Jun 1
暂无{DOI}: 10.7518/hxkq.2024.2023416
{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) 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.
目的: 研究舌黏膜癌变过程中基因组甲基化特征,探讨舌癌中DNA甲基化的规律。方法: 用50 mg/L的4-硝基喹啉-1-氧化物(4NQO)饮水诱导C57BL/6J小鼠舌黏膜癌变,分别取第0、12、28周的舌黏膜(分别代表正常、癌前病变和癌变)进行基因芯片检测和甲基化DNA免疫沉淀测序(MeDIP-Seq),在人舌黏膜组织和人舌癌细胞系中,用实时定量逆转录聚合酶链反应(qRT-PCR)和飞行质谱检测验证转化生长因子贝塔信号蛋白1(SMAD1)的表达和启动子的甲基化。结果: 28周较12周和0周舌黏膜的胞嘧啶鸟嘌呤岛(CGI)甲基化水平均升高,12周时启动子甲基化水平高于0周。在0、12和28周期间,208个差异表达基因与启动子中的差异甲基化呈负相关。与正常黏膜相比,细胞系中SMAD1的mRNA上调,同时启动子甲基化水平降低。结论: 舌黏膜癌变中伴随DNA甲基化修饰异常,舌癌中SMAD1高表达伴启动子低甲基化。.