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Screening therapeutic targets of ribavirin in hepatocellular carcinoma
Chen Xu1, Liyun Luo2, Yongjun Yu1
1Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, P.R. China.
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.
Insights
This study identifies key microRNAs (miRNAs) and messenger RNAs (mRNAs) involved in ribavirin treatment for hepatocellular carcinoma (HCC). These findings suggest novel therapeutic targets for HCC, including specific miRNAs and mRNAs like CCNB1 and DEPDC1.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Identifying molecular mechanisms underlying drug responses is crucial for effective HCC treatment.
Purpose of the Study:
- To screen key genes affected by ribavirin in hepatocellular carcinoma (HCC).
- To identify novel therapeutic targets for HCC treatment based on molecular interactions.
Main Methods:
- Utilized mRNA and miRNA expression datasets (GSE23031, GSE74656, GSE22058) from the Gene Expression Omnibus database.
- Applied differential expression analysis using the limma package in R.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
- Identified miRNA-mRNA interactions using TargetScan.
Main Results:
- Identified 559 differentially expressed genes (DEGs) in ribavirin-treated HCC cells (DEG-Ribavirin) and 632 DEGs in HCC tissues (DEG-Tumor).
- Detected 220 differentially expressed miRNAs in HCC tissues.
- Uncovered five key miRNA-mRNA regulatory pairs, including miR-96 targeting DEPDC1 and CCNB1, and miR-183 targeting CCNB1 and NTN4.
Conclusions:
- Specific miRNAs (miR-96, miR-145, miR-183) and mRNAs (NAT2, FBXO5, CCNB1, DEPDC1, NTN4) are associated with ribavirin's effects on HCC.
- These identified molecules represent potential novel therapeutic targets for hepatocellular carcinoma treatment.
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