Screening of molecular targets and construction of a ceRNA network for oxaliplatin resistance in colorectal cancer

Abstract

Oxaliplatin resistance reduces the efficacy of chemotherapy for colorectal cancer (CRC). This study aimed to screen molecular targets of oxaliplatin resistance in CRC to construct a ceRNA network. The differentially expressed mRNA and lncRNA between the oxaliplatin-resistant and oxaliplatin-sensitive colon cancer cell lines was determined using RNA sequencing data (no. GSE42387) from the NCBI GEO database. Gene Ontology BP (biological process) and KEGG pathway enrichment analyses were used to analyze the function and pathway enrichment of the differentially expressed mRNA and lncRNA. The lnCeDB and starBase v2.0 were used to predict miRNA, and Cytoscape software was used to build a ceRNA network. The top 5 mRNA, miRNAs, and lncRNAs with high degrees of connectivity in the ceRNA network were validated by qPCR. TCGA colon cancer clinical data was used to perform a survival analysis of patients with differential mRNA and lncRNA expression. Between the two groups, 2515 mRNAs and 23 lncRNAs were differentially expressed. We constructed a ceRNA network containing 503 lncRNA-miRNA-mRNA regulatory pairs, 210 lncRNA-miRNA pairs, 382 miRNA-mRNA pairs, and 212 mRNA co-expression pairs. The differentially expressed lncRNA, miRNA and mRNA were verified by qPCR. One lncRNA (HOTAIR) and 14 mRNAs significantly correlated with patient prognosis. The discovery of differentially expressed genes and the construction of ceRNA networks will provide important resources for the search for therapeutic targets of oxaliplatin resistance. Moreover, this resource will aid the discovery of the mechanisms behind this type of drug resistance.