Screening therapeutic targets of ribavirin in hepatocellular carcinoma.

Abstract

The objective of the present study was to screen the key genes of ribavirin in hepatocellular carcinoma (HCC) and provide novel therapeutic targets for HCC treatment. The mRNA expression datasets of GSE23031 and GSE74656, as well as the microRNA (miRNA) expression dataset of GSE22058 were downloaded from the Gene Expressed Omnibus database. In the GSE23031 dataset, there were three HCC cell lines treated with PBS and three HCC cell lines treated with ribavirin. In the GSE74656 dataset, five HCC tissues and five carcinoma adjacent tissues were selected. In the GSE22058 dataset, 96 HCC tissues and 96 carcinoma adjacent tissues were selected. The differentially expressed genes (DEGs) and differentially expressed miRNAs were identified via the limma package of R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed with the Database for Annotation, Visualization and Integrated Discovery. The target mRNAs of DEMs were obtained with TargetScan. A total of 559 DEGs (designated DEG-Ribavirin) were identified in HCC cells treated with ribavirin compared with PBS and 632 DEGs (designated DEG-Tumor) were identified in HCC tissues compared with carcinoma adjacent tissues. A total of 220 differentially expressed miRNAs were identified in HCC tissues compared with carcinoma adjacent tissues. In addition, 121 GO terms and three KEGG pathways of DEG-Ribavirin were obtained, and 383 GO terms and 25 KEGG pathways of DEG-Tumor were obtained. A total of five key miRNA-mRNA regulated pairs were identified, namely miR-183→CCNB1, miR-96→DEPDC1, miR-96→NTN4, miR-183→NTN4 and miR-145→NTN4. The present study indicated that certain miRNAs (including miR-96, miR-145 and miR-183) and mRNAs (including NAT2, FBXO5, CCNB1, DEPDC1 and NTN4) may be associated with the effects of ribavirin on HCC. Furthermore, they may provide novel therapeutic targets for HCC treatment.