Chronic hepatitis B virus (HBV) infection is one of the most associated factors in hepatocarcinogenesis. HBV is able to integrate into the host genome and encode the multi-functional hepatitis B virus x protein (HBx). Although the mechanism between HBx and carcinogenesis is still elusive, recent studies have shown that HBx was able to influence various signaling pathways, as well as epigenetic and genetic processes. This review will examine and summarize recent literature about HBx’s role in these various processes.

Hepatocellular carcinoma (HCC) is a common cancer and the sixth most lethal malignancy in the world. We chose gene expression profile of GSE14520 from GEO database aiming to find key genes that affect HCC progression. 22 paired tumor and non-tumor samples were included in this analysis.Differentially expressed genes (DEGs) between tumor and non-tumor were selected using GEO2R. Gene ontology (GO) enrichment and protein-protein interaction (PPI) of the DEGs were done using Metascape. There were 357 DEGs, including 70 up-regulated genes and 287 down-regulated genes. These DEGs were enriched in drug metabolic process, organic acid catabolic process, monocarboxylic metabolic process and etc. Three important modules were detected from PPI network using Molecular Complex Detection (MCODE) algorithm. Moreover, the Kaplan-Meier analysis for overall survival and disease-free survival were applied to those genes in top PPI group. In conclusion, this bioinformatic analysis demonstrated that DEGs, such as CYP2C9, might promote the development of HCC, especially in drug metabolism. It could also be used as a new biomarker for diagnosis.

FAT10, which is also known as diubiquitin, has been implicated to play important roles in immune regulation and tumorigenesis. Its expression is up-regulated in the tumors of Hepatocellular Carcinoma (HCC) and other cancer patients. High levels of FAT10 in cells have been shown to result in increased mitotic non-disjunction and chromosome instability, leading to tumorigenesis. To evaluate whether the aberrant up-regulation of the FAT10 gene in the tumors of HCC patients is due to mutations or the aberrant methylation of CG dinucleotides at the FAT10 promoter, sequencing and methylation-specific sequencing of the promoter of FAT10 was performed. No mutations were found that could explain the differential expression of FAT10 between the tumor and non-tumorous tissues of HCC patients. However, six single nucleotide polymorphisms (SNPs), including one that has not been previously reported, were identified at the promoter of the FAT10 gene. Different haplotypes of these SNPs were found to significantly mediate different FAT10 promoter activities. Consistent with the experimental observation, differential FAT10 expression in the tumors of HCC patients carrying haplotype 1 was generally higher than those carrying haplotype II. Notably, the methylation status of this promoter was found to correlate with FAT10 expression levels. Hence, the aberrant overexpression of the FAT10 gene in the tumors of HCC patients is likely due to aberrant methylation, rather than mutations at the FAT10 promoter.