Construction and Bioinformatics analysisof competing endogenous RNA (ceRNA) regulation networkin colorectal cancer

Background: Among men and women, colorectal cancer(CRC) rates are third for incidence and second for cancer-relatedmortality. According to the ceRNA hypothesis, circRNAsmay function as ceRNAs in cancers by interacting with miRNAs.Despite this, it is still unclear how the circRNA/miRNA/mRNA ceRNA regulatory network contributes to CRC development Materials and Methods: In this study, the R Limma packagewas used to identify differentially expressed circRNAs (DECs)from four GEO microarray datasets (GSE۱۲۶۰۹۴, GSE۱۳۸۵۸۹,GSE۱۴۲۸۳۷, GSE۱۲۱۸۹۵). R DESeq۲ package was also usedto identify differentially expressed miRNAs (DEMIs) and mRNAs(DEGs) in colon adenocarcinoma (COAD). The secondstep involved determining DECs' binding sites using the CSCDwebsite. The intersection of predicted miRNAs from CSCD andDEMIs from TCGA revealed DECs' potential targets. Throughthe intersection of dysregulated DEGs with targeted genes predictedby miRDB online tools, candidate genes were identifiedas the third step. A network of ceRNA was then built in Cytoscape.The R ClusterProfiler package was employed for functionalenrichment, and Cytoscape's STRING plugin was used tobuild the PPI network. Additionally, by the CytoHubba plugin,ten hub genes in the PPI network were detected. The final stepsincluded analyzing immune cell infiltration and overall survivalof ten hub genes to constructing the final ceRNA network andidentifying ceRNA axes.Results: Two DECs were identified in our analysis, hsa_circ_۰۰۰۰۵۱۹ and hsa_circ_۰۰۸۷۸۶۲, which regulate twelvemiRNAs. As a result of these predictions, ۷۲۸ genes are predictedto be regulated by the twelve miRNAs. Most of thesegenes are associated with cancer-related regulatory pathwaysbased on functional enrichment analysis. The PPI network wasconstructed for these genes, and after removing unconnectednodes, ۱۴۳ genes were screened. From this network, ten hubgenes were identified (CD۴, IL۱B, CXCL۱۰, FOXP۳, VEGFA,CD۴۴, CCR۲, IL۱A, CSF۳, and CSF۱). CD۴, FOXP۳, CCR۲,and CSF۱ were significantly related to all inflammatory immunefactors, and IL۱A and IL۱B are significantly associatedwith overall survival. Two DECs, six miRNAs, and six hubgenes were combined as a final ceRNA network (FceRNET) bythe Sankey plot. From this FceRNET, three ceRNA axes wereidentified.Conclusion: Our study suggests that ceRNA axes includinghsa_circ_۰۰۰۰۵۱۹/hsa-miR-۱۵۰-۵p/IL۱A, hsa_circ_۰۰۰۰۵۱۹/hsa-miR-۲۹۶-۵p/CD۴۴, and hsa_circ_۰۰۸۷۸۶۲/hsa-miR-۳۱۲۷-۵p/FOXP۳ may play important roles in the pathogenesis ofCRC, and might also serve as potential biomarkers for diagnosisand prognosis of CRC.