Comprehensive analysis of microRNA/mRNA signature in colon adenocarcinoma

OBJECTIVE: The goal of our study was to identify the regulatory mechanisms of gene expression mediated by miRNAs and DNA methylation in colon adenocarcinoma (COAD).

MATERIALS AND METHODS:  The miRNAs and mRNAs expression and DNA methylation data of COAD and adjacent normal tissues were obtained from The Cancer Genome Atlas (TCGA) database. Based on the differentially expressed miRNAs and mRNAs, miRNA-mRNA pairs were obtained by correlation analysis and prediction algorithms. Finally, COAD-specific miRNA-mRNA regulatory network was generated. Additionally, the biological functions of miRNA targets were further revealed by GO and KEGG enrichment analysis. Besides, the correlation analysis between gene expression and DNA methylation was also performed after differential analysis.

RESULTS: We identified 55 differentially expressed miRNAs and 1291 differentially expressed mRNAs in COAD compared with adjacent normal tissues. We observed a global miRNA up-regulation in tumors. A total of 58 miRNA-mRNA pairs were not only predicted by algorithms but also negatively correlated. The increased expression of has-mir-141, -19a, -20a 19b-1, 19b-2, 16, 590 and -335 were closely associated with the carcinogenesis of COAD. Functional enrichment analysis showed that the miRNA targets were significantly enriched in pancreatic secretion, salivary secretion, gastric acid secretion and bile secretion. Regarding the regulatory role of DNA methylation, we identified 11 genes whose expressions were negatively correlated with DNA methylation level. Among those genes, MSX1 and KRT7 were down-regulated and hypermethylated in COAD compared with adjacent normal tissues.

CONCLUSIONS: These eight miRNAs (has-mir-141, -19a, -20a 19b-1, 19b-2, 16, 590 and -335) and two genes (MSX1 and KRT7) may play a role in the process of COAD. These findings highlighted the potential regulatory mechanisms of miRNA and DNA methylation on mRNA expression in COAD carcinogenesis.

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