MicroRNA mediated network and DNA methylation in colorectal cancer.

Colorectal cancer (CRC) is one of the most malignant cancers. A growing number of studies have shown that both genetic and epigenetic play important roles in the etiology of CRC. Both microRNA (miRNA) and DNA methylation belong to the scope of epigenetic and there are complex regulatory mechanisms within miRNA and DNA methylation. We compiled 71 CRC related genes and 134 CRC related miRNAs. Then we identified 417 feed forward loops (FFLs) and 37 feedback loops (FBLs) among these genes, miRNAs and transcription factors (TFs). We constructed a network of miRNAs and TFs mediation for CRC utilizing these FFLs and FBLs. Statistical tests proved that these FFLs were significantly enriched in the CRC comparing to the esophageal cancer, breast cancer and randomly selected CRCmiRNA-gene pairs. Analysis of the network singled out 3 core genes, 2 core miRNAs and 5 core TFs. The KEGG enrichment and GO enrichment for the 2 core miRNA target genes indicated that they were significantly enriched in CRC related pathways. (Ex. MARK pathway, TGFβ pathway and cell cycle) Through the investigation on methylation, we found that most of the CRC related genes and miRNAs were prone to be regulated by methylation. This study sheds lights on the regulatory mechanisms in CRC and we provide some insights on the epigenetic of CRC.