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Role of ceRNA Regulatory Network in Colorectal Cancer Based on Bioinformatics |
(Department of Gastroenterolody, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China) |
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Abstract Abstract: To explore the regulatory mechanisms of the competing endogenous RNA (ceRNA) network associated with colorectal cancer (CRC) and to find potential targets for CRC treatment, The CRC-related circRNA datasets were downloaded from the Gene Expression Omnibus (GEO) database, differentially expressed circRNAs were screened using the robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) analysis. Real-time fluorogenic quantitative PCR (RT-qPCR) was used to verify that screened circRNAs (hsa_circRNA_057090, hsa_circRNA_092566) were circular and both highly expressed in CRC tissues and CRC cell lines. And miRNAs bound to circRNAs were predicted on the circBank and CircInteractome databases. Target genes of miRNAs were predicted on the TargetScan and miRDB databases, differentially expressed mRNAs in CRC were screened on The Cancer Genome Atlas (TCGA) databases, after intersection, differentially expressed target genes were recognized. Then, the ceRNA regulatory network was constructed. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, protein interaction network construction, and survival analysis were performed on target genes using DAVID software, String database, Cytoscape software, and Gene Expression Profiling Interactive Analysis (GEPIA) database, respectively. Ten core genes were identified from PPI network containing 427 mRNAs. Finally, the circRNA-miRNA-coregene network was constructed. GO enrichment analysis and KEGG enrichment analysis showed that core genes were mainly involved in chemical synaptic transmission, ion transmembrane transport and were significantly enriched in several signaling pathways, such as cAMP. Survival analysis showed that the expression levels of two core genes SNAP25, ATP2B2 were significantly correlated with the prognosis of CRC patients. The hsa_circRNA_057090, hsa_circRNA_092566 identified and ceRNA network constructed might provide novel biomarkers or potential therapeutic targets for CRC.
Key words: colorectal cancer; circRNA; ceRNA; core gene network; treatment targets
(Acta Laser Biology Sinica, 2024, 33(4): 365-376)
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