Abstract

BackgroundHepatocellular carcinoma (HCC) is the leading cause of cancer mortality. Chemical and virus induction are two major risk factors, however, the potential molecular mechanisms of their differences remain elusive. In this study, to identify the similarities and differences between chemical and virus induced HCC models, we compared the gene expression profiles between DEN and HBx mice models, as well as the differences among tumor, para-tumor and normal tissues.MethodsWe sequenced both gene and microRNA (miRNA) expression for HCC tumor tissues, para-tumor and normal liver tissues from DEN model mice (30-week-old) and downloaded the corresponding microarray expression data of HBx model from GEO database. Then differentially expressed genes (DEGs), miRNAs and transcription factors (TFs) were detected by R packages and performed functional enrichment analysis. To explore the gene regulatory network in HCC models, miRNA and TF regulatory networks were constructed by target prediction.ResultsFor model comparison, although DEGs between tumor and normal tissues in DEN and HBx models only had a small part of overlapping, they shared common pathways including lipid metabolism, oxidation-reduction process and immune process. For tissue comparisons in each model, genes in oxidation-reduction process were down-regulated in tumor tissues and genes in inflammatory response showed the highest expression level in para-tumor tissues. Genes highly expressed in both tumor and para-tumor tissues in two models mainly participated in immune and inflammatory response. Genes expressed in HBx model were also involved in cell proliferation and cell migration etc. Network analysis revealed that several miRNAs such as miR-381-3p, miR-142a-3p, miR-214-3p and TFs such as Egr1, Atf3 and Klf4 were the core regulators in HCC.ConclusionsThrough the comparative analyses, we found that para-tumor tissue is a highly inflammatory tissue while the tumor tissue is specific with both inflammatory and cancer signaling pathways. The DEN and HBx mice models have different gene expression pattern but shared pathways. This work will help to elucidate the molecular mechanisms underlying different HCC models.

Highlights

  • Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality

  • The cumulative distribution of genes in DEN and Hepatitis B virus X antigen (HBx) models and functions of highly expressed genes in tumor In this study, a total of 20,901 genes were detected by high-throughput sequencing in DEN model, and 23,855 genes were identified in HBx model microarray data

  • In DEN model, the log10 (FPKM) of 95% genes are less than 1.43 while in HBx model the log10 of 95% genes are less than 3.94

Read more

Summary

Introduction

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality. To identify the similarities and differences between chemical and virus induced HCC models, we compared the gene expression profiles between DEN and HBx mice models, as well as the differences among tumor, para-tumor and normal tissues. Hepatocellular carcinoma (HCC) accounts for 85 - 90% of liver malignancies and is the second cause of cancer death in the world [1]. HCC is often arisen by several risk factors including hepatitis virus B or C (HBV or HCV) infection, chemical damage and chronic excessive alcohol intake and so on [3]. The HBx (HBV regulatory x protein) of hepatitis B virus plays a crucial role in hepatocarcinogenesis by transcriptional activation, driving deregulated cell cycle progression, modulation of apoptosis and inhibition of nucleotide excision repair of damaged cellular DNA [5]. The differences of gene expression and regulation in these two HCC models have not been compared, which is an important issue for model selection in HCC studies

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call