Integrated analysis of DNA methylation and microRNA regulation of the lung adenocarcinoma transcriptome.

Lung adenocarcinoma, as a common type of non-small cell lung cancer (40%), poses a significant threat to public health worldwide. The present study aimed to determine the transcriptional regulatory mechanisms in lung adenocarcinoma. Illumina sequence data GSE 37764 including expression profiling, methylation profiling and non-coding RNA profiling of 6 never-smoker Korean female patients with non-small cell lung adenocarcinoma were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated genes, differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) between normal and tumor tissues of the same patients were screened with tools in R. Functional enrichment analysis of a variety of differential genes was performed. DEG-specific methylation and transcription factors (TFs) were analyzed with ENCODE ChIP-seq. The integrated regulatory network of DEGs, TFs and miRNAs was constructed. Several overlapping DEGs, such as v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) were screened. DEGs were centrally modified by histones of tri-methylation of lysine 27 on histone H3 (H3K27me3) and di-acetylation of lysine 12 or 20 on histone H2 (H2BK12/20AC). Upstream TFs of DEGs were enriched in different ChIP-seq clusters, such as glucocorticoid receptors (GRs). Two miRNAs (miR-126-3p and miR-30c-2-3p) and three TFs including homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1) and T-box 5 (TBX5), played important roles in the integrated regulatory network conjointly. These DEGs, and DEG-related histone modifications, TFs and miRNAs may be important in the pathogenesis of lung adenocarcinoma. The present results may indicate directions for the next step in the study of the further elucidation and targeted prevention of lung adenocarcinoma.