Abstract
This study aims to lay a foundation for studying the regulation of microRNAs (miRNAs) in colon cancer by applying bioinformatics methods to identify miRNAs and their potential critical target genes associated with colon cancer and prognosis. Data of differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from two independent databases (TCGA and GEO) and analyzed by R software resulted in 472 DEMs and 565 DEGs in colon cancers, respectively. Next, we developed an 8-miRNA (hsa-mir-6854, hsa-mir-4437, hsa-mir-216a, hsa-mir-3677, hsa-mir-887, hsa-mir-4999, hsa-mir-34b, and hsa-mir-3189) prognostic signature for patients with colon cancer by Cox proportional hazards regression analysis. To predict the target genes of these miRNAs, we used TargetScan and miRDB. The intersection of DEGs with the target genes predicted for these eight miRNAs retrieved 112 consensus genes. GO and KEGG pathway enrichment analyses showed these 112 genes were mainly involved in protein binding, one-carbon metabolic process, nitrogen metabolism, proteoglycans in cancer, and chemokine signaling pathways. The protein–protein interaction network of the consensus genes, constructed using the STRING database and imported into Cytoscape, identified 14 critical genes in the pathogenesis of colon cancer (CEP55, DTL, FANCI, HMMR, KIF15, MCM6, MKI67, NCAPG2, NEK2, RACGAP1, RRM2, TOP2A, UBE2C, and ZWILCH). Finally, we verified the critical genes by weighted gene co-expression network analysis (WGCNA) of the GEO data, and further mined the core genes involved in colon cancer. In summary, this study identified an 8-miRNA model that can effectively predict the prognosis of colon cancer patients and 14 critical genes with vital roles in colon cancer carcinogenesis. Our findings contribute new ideas for elucidating the molecular mechanisms of colon cancer carcinogenesis and provide new therapeutic targets and biomarkers for future treatment and prognosis.
Highlights
Colon cancer is one of the common malignant tumors of the digestive tract and occurs in the colon
According to a criterion larger than twice the average, we identified 16 candidate hub genes: CCND1, centrosomal protein 55 (CEP55), Denticleless E3 ubiquitin–protein ligase homolog (DTL), FANCI, hyaluronan-mediated motility receptor (HMMR), Kinesin family member 15 (KIF15), maintenance complex component 6 (MCM6), marker of proliferation Ki-67 (MKI67), MYC, non-SMC condensin II complex subunit G2 (NCAPG2), NIMA-related kinase 2 (NEK2), Rac GTPase activating protein 1 (RACGAP1), regulatory subunit M2 (RRM2), DNA topoisomerase II alpha (TOP2A), ubiquitin-conjugating enzyme E2C (UBE2C), and Zwilch kinetochore protein (ZWILCH) (Figure 5B)
Our results identified FANCI and ZWILCH as critical target genes of colon cancer, suggesting that they might provide a potential pathway for the treatment and intervention of colon cancer
Summary
Colon cancer is one of the common malignant tumors of the digestive tract and occurs in the colon. With the development of the economy and the improvement of people’s living standards, the incidence of colon cancer in recent years has increased, and the age of onset lowered, posing a serious threat to people’s life and health (Arnold et al, 2017). Patients with colon cancer have no specific clinical symptoms in the early stage (Cappell, 2008). Most of the deaths of colon cancer patients are a result of tumor metastasis (Siegel et al, 2017). It is necessary to identify new biomarkers and find potential therapeutic targets for early detection and treatment of colon cancer through effective strategies
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