Mechanism analysis of colorectal cancer according to the microRNA expression profile

Abstract

The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were analyzed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the target genes was constructed using the Search Tool for the Retrieval of Interacting Genes database. The present study identified a total of 18 differentially expressed miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126) and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC developmental pathway. All these target genes had higher node degrees in the PPI network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular mechanisms for the progression of CRC.

Keywords: colorectal cancer; microRNAs; pathway analysis; protein-protein interaction network analysis; target genes.

Figure 1.

Upregulated miR-target gene interactions. Red triangles represent miRs and pink ovals represent their target genes. The lines demonstrate the associations between the miRs and the target genes. miR, microRNA.

Figure 2.

Downregulated miR-target gene interactions. Red triangles represent miRs and green ovals represent their target genes. The lines demonstrate the associations between the miRs and the target genes. miR, microRNA.

Figure 3.

Protein to protein interaction network of differentially expressed miR target genes. Pink ovals represent target genes corresponding to upregulated miRs and green ovals represent target genes corresponding to downregulated miRs. The lines demonstrate the interaction between target genes. miR, microRNA.