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.

Systematic analysis of the expression and prognosis relevance of FBXO family reveals the significance of FBXO1 in human breast cancer

“…FBXO5 has been suggested to play crucial roles in the development of HCC, cervical cancer and squamous-cell lung carcinoma in the latest research on bioinformatics analysis [46][47][48]. Also, we got the similar results in BC.…”

Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for hepatocellular carcinoma

“…In glioblastoma, anti-miR-182 expression results in increased expression of biomarkers for proliferation and stem cell biomarkers (e.g., CCNB1, CD44, Sox2, and Nestin) [45]. Xu et al reported that hsa-miR-183/CCNB1 may be related to the effect of ribavirin on HCC [46]. Therefore, we believe that the hsa-miR-182/CHL1 and hsa-miR-183/CCNB1 axes may have a strong influence on HCC pathogenesis and may provide novel therapeutic targets for HCC treatment.…”

Anticancer Effects of Gleditsia sinensis Extract in Rats Transplanted With Hepatocellular Carcinoma Cells

“…HCC is known to express important amounts of miR-183 18 . The Wnt/β-catenin pathway could activate miR-183 expression in HCC to promote cell invasion 19 , and miR-183 also inhibits TGF-β1-induced apoptosis in HCC tumor cells 16 .…”