Identification of MicroRNA-Target Gene-Transcription Factor Regulatory Networks in Colorectal Adenoma Using Microarray Expression Data

OBJECTIVE: The aim of the study was to find the key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct miRNA-target gene-TF regulatory networks to investigate the underlying molecular mechanism in colorectal adenoma (CRA). METHODS: Four mRNA expression datasets and one miRNA expression dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were identified between CRA and normal samples. Moreover, functional enrichment analysis for DEGs was carried out utilizing the Cytoscape-plugin, known as ClueGO. These DEGs were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then, a miRNA-target gene regulatory network was established to screen key DEMs. In addition, similar workflow of the analyses were also performed comparing the CRC samples with CRA ones to screen key DEMs. Finally, miRNA-target gene-TF regulatory networks were constructed for these key DEMs using iRegulon plug-in in Cytoscape. RESULTS: We identified 514 DEGs and 167 DEMs in CRA samples compared to healthy samples. Functional enrichment analysis revealed that these DEGs were significantly enriched in several terms and pathways, such as regulation of cell migration and bile secretion pathway. A PPI network was constructed including 325 nodes as well as 890 edges. A total of 59 DEGs and 65 DEMs were identified in CRC samples compared to CRA ones. In addition, Two key DEMs in CRA samples compared to healthy samples were identified, such as hsa-miR-34a and hsa-miR-96. One key DEM, hsa-miR-29c, which was identified when we compared the differentially expressed molecules found in the comparison CRA versus normal samples to the ones obtained in the comparison CRC versus CRA, was also identified in CRC samples compared to CRA ones. The miRNA-target gene-TF regulatory networks for these key miRNAs included two TFs, one TF and five TFs, respectively. CONCLUSION: These identified key genes, miRNA, TFs and miRNA-target gene-TF regulatory networks associated with CRA, to a certain degree, may provide some hints to enable us to better understand the underlying pathogenesis of CRA.