Zhao Shuang, Zhang Ye, Liang Xujun, Li Maoyu, Peng Fang, Chen Zhuchu, Chen Yongheng
Key Laboratory of Cancer Proteomics of National Health Commission, Xiangya Hospital, Central South University, Changsha 410008, China.
Anticancer Agents Med Chem. 2019;19(6):772-782. doi: 10.2174/1871520619666190204094815.
DNA methylation, which acts as an expression regulator for multiple Tumor Suppressor Genes (TSGs), is believed to play an important role in Nasopharyngeal Carcinoma (NPC) development.
We compared the effects of 5-aza-2-deoxycytidine (decitabine, DAC) on gene expression using RNA sequencing in NPC cells.
We analyzed Differentially Expressed Genes (DEGs) in NPC cells using DAC demethylation treatment and found that 2182 genes were significantly upregulated (≥ 2-fold change), suggesting that they may play a key role in cell growth, proliferation, development, and death. For data analysis, we used the Gene Ontology database and pathway enrichment analysis of the DEGs to discover differential patterns of DNA methylation associated with changes in gene expression. Furthermore, we evaluated 74 methylated candidate TSGs from the DEGs in NPC cells and summarized these genes in several important signaling pathways frequently disrupted by promoter methylation in NPC tumorigenesis.
Our study analyzes the DEGs and identifies a set of genes whose promoter methylation in NPC cells is reversed by DAC. These genes are potential substrates of DNMT inhibitors and may serve as tumor suppressors in NPC cells.
DNA甲基化作为多种肿瘤抑制基因（TSGs）的表达调节因子，被认为在鼻咽癌（NPC）的发生发展中起重要作用。
我们使用RNA测序比较了5-氮杂-2'-脱氧胞苷（地西他滨，DAC）对NPC细胞基因表达的影响。
我们使用DAC去甲基化处理分析了NPC细胞中的差异表达基因（DEGs），发现2182个基因显著上调（≥2倍变化），表明它们可能在细胞生长、增殖、发育和死亡中起关键作用。为了进行数据分析，我们使用基因本体数据库和DEGs的通路富集分析来发现与基因表达变化相关的DNA甲基化差异模式。此外，我们评估了NPC细胞中DEGs的74个甲基化候选TSGs，并在NPC肿瘤发生过程中经常因启动子甲基化而被破坏的几个重要信号通路中总结了这些基因。
我们的研究分析了DEGs，并鉴定出一组基因，其在NPC细胞中的启动子甲基化被DAC逆转。这些基因是DNA甲基转移酶抑制剂的潜在底物，可能在NPC细胞中作为肿瘤抑制因子发挥作用。
