Functional analysis of DNA methylation in lung cancer

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.