The aim of this study was to elucidate the role of DNA methylation-silenced genes in malignant transformation. We screened DNA methylation-silenced genes during methacrylate (GMA)-induced malignant transformation of human bronchial epithelial cells (16HBE) by DNA methylation microarray analysis. The methylation status of some identified genes was assessed by a polymerase chain reaction and compared with uninduced control cells. A total of 801, 66 and 30 genes were silenced in 10th, 20th and 30th generation cells; 8 genes were silenced in 10th and 20th generation cells but not in 30th generation cells; 14 genes were silenced in 30th and 10th generation cells but not in 20th generation cells; and one gene was silenced in 20th and 30th generation cells but not in 10th generation cells. TRPV1 and SOD2 genes were methylated and their gene expression levels were significantly lower in 30th generation 16HBE cells treated with GMA compared to uninduced control cells (P < 0.05). The expression levels of DNA methylation-silenced genes were altered throughout the GMA-induced malignant transformation of 16HBE cells. Furthermore, TRPV1/SOD2 may represent a specific molecular marker associated with the malignant transformation of GMA-stimulated 16HBE cells.

本研究的目的是阐明 DNA 甲基化沉默基因在恶性转化中的作用。我们通过 DNA 甲基化微阵列分析在甲基丙烯酸酯 (GMA) 诱导的人支气管上皮细胞 (16HBE) 恶性转化过程中筛选了 DNA 甲基化沉默的基因。一些已鉴定基因的甲基化状态通过聚合酶链反应进行评估，并与未诱导的对照细胞进行比较。第10代、20代和30代细胞共有801、66和30个基因被沉默；8个基因在第10代和第20代细胞中被沉默，但在第30代细胞中没有；14个基因在第30代和第10代细胞中被沉默，但在第20代细胞中没有；一个基因在第 20 代和第 30 代细胞中被沉默，但在第 10 代细胞中没有。TRPV1和SOD2与未诱导的对照细胞相比，GMA 处理的第 30 代 16HBE 细胞基因甲基化且基因表达水平显着降低（P  < 0.05）。在 GMA 诱导的 16HBE 细胞恶性转化过程中，DNA 甲基化沉默基因的表达水平发生了改变。此外，TRPV1/SOD2可能代表与 GMA 刺激的 16HBE 细胞恶性转化相关的特定分子标记。