Department of Cardiothoracic Surgery, Changhai Hospital, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2013 May;17(9):1191-7.
We aimed to explore the DNA methylation difference between lung cancer samples and non-cancer lung samples, and to investigate the role of DNA methylation in the mechanism of lung cancer development. Besides, we analyzed the transcriptional regulation network of DNA methylation and the miRNAs regulated by DNA methylation. This study provides a framework for DNA methylation in other tumors or diseases.
DNA methylation and gene expression profiles used were obtained from Gene Expression Omnibus. Firstly, we identified differentially methylated genes (DMGs) by Student's t-test. Then we detected the biological processes and pathways changed in lung cancer by Gene Ontology (GO) and KEGG pathway enrichment analysis. The transcriptional factors in differential genes were identified and the microRNAs regulated by them were also obtained in TransmiR.
We obtained 108 DMGs between lung cancer samples and non-cancer samples. Besides development related biological processes and pathways were dramatically disordered. For the DMGs, we identified 11 transcriptional factors regulating them. Moreover, we screened out 21 relationships between DMGs and their transcriptional targets. Five microRNAs are reported to be regulated by DNA methylation genes. Finally a regulation network of DNA methylation was constructed.
DNA methylation participates in carcinogenesis at the transcriptional and post-transcriptional level. Aberrant DNA methylation will prevent its binding with the upstream regulatory proteins, inhibit the function of downstream target genes and regulate the expression of downstream miRNA, and consequently affect cell development, immunoresponse and apoptosis.
探索肺癌样本与非癌肺样本之间的 DNA 甲基化差异，研究 DNA 甲基化在肺癌发生机制中的作用。此外，还分析了 DNA 甲基化的转录调控网络以及受 DNA 甲基化调控的 miRNAs。本研究为其他肿瘤或疾病中的 DNA 甲基化提供了研究框架。
使用的 DNA 甲基化和基因表达谱数据均来自基因表达综合数据库。首先，我们通过学生 t 检验来识别差异甲基化基因（DMGs）。然后，我们通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析检测肺癌中改变的生物过程和通路。鉴定差异基因中的转录因子，并在 TransmiR 中获得受其调控的 microRNAs。
我们在肺癌样本和非癌样本之间获得了 108 个 DMGs。此外，与发育相关的生物过程和通路也出现了明显紊乱。对于这些 DMGs，我们鉴定出了 11 个调节它们的转录因子。此外，我们还筛选出了 21 个 DMGs 与其转录靶标之间的关系。有 5 个 microRNAs 被报道受 DNA 甲基化基因的调控。最后构建了一个 DNA 甲基化调控网络。
DNA 甲基化在转录和转录后水平参与了致癌作用。异常的 DNA 甲基化会阻止其与上游调节蛋白结合，抑制下游靶基因的功能，并调节下游 miRNA 的表达，从而影响细胞发育、免疫反应和细胞凋亡。
