A Pleiotropic Role of the Hepatitis B Virus Core Protein in Hepatocarcinogenesis

Abstract

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC), which is the sixth most prevalent cancer among all cancers worldwide. However, the pathogenesis of HBV-mediated hepatocarcinogenesis is unclear. Evidence currently available suggests that the HBV core protein (HBc) plays a potential role in the development of HCC, such as the HBV X protein. The core protein, which is the structural component of the viral nucleocapsid, contributes to almost every stage of the HBV life cycle and occupies diverse roles in HBV replication and pathogenesis. Recent studies have shown that HBc was able to disrupt various pathways involved in liver carcinogenesis: the signaling pathways implicated in migration and proliferation of hepatoma cells, apoptosis pathways, and cell metabolic pathways inducing the development of HCC; and the immune system, through the expression and production of proinflammatory cytokines. In addition, HBc can modulate normal functions of hepatocytes through disrupting human host gene expression by binding to promoter regions. This HBV protein also promotes HCC metastasis through epigenetic alterations, such as micro-RNA. This review focuses on the molecular pathogenesis of the HBc protein in HBV-induced HCC.

Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis

“…Transcription factor (TF) prediction has revealed that a variety of TF are involved in the regulation of hub genes expression (Figure 11A), and it was identified in the internal data set that high expression of 9 TFs and low expression of 5 TFs may be important causes of abnormal changes in hub genes (Figure S5). Because the module gene is closely related to RNA methylation (Figure 4A), the hub genes was predicted by m 6 A methylation and verified by internal data sets. The results showed that the hub genes were regulated by m 6 A writer and reader proteins (Figures 11B, S6).…”

“…For target-based drug reuse, the ara-CTP and guanosine trip can form multi-hydrogen-bond complexes with POL2B, RPS6 and RPL23A, with low binding energy, suggesting that they may have a better prognosis when used as adjuvant therapy for patients with virus-associated HCC, which is clear from the results. For the regulation of expression of hub genes, it was speculated that abnormal expression of 14 transcription factors associated with high expression of hub genes through database and internal validation, and the m 6 A enzyme may play an important role in post-transcriptional modification. In conclusion, this study identified the novel molecules involved in virus-associated HCC, which can provide a reference for the diagnosis and treatment of patient.…”

“…In theory, the persistent inflammation of hepatocytes caused by viral infection promotes the formation of hepatic fibrosis, which is the basis for the development of HCC (5). Chronic infection caused by HBV to the human body, and chronic hepatitis B, compensated cirrhosis, and decompensated cirrhosis to the onset of HCC are the main pathways for the development of HBV-associated HCC (HBV-HCC) (6). It has been found that the HBx protein carried by HBV can regulate the PI3K-Akt pathway of host hepatocytes, and then activate and release of excessive TGF-b to participate in the occurrence of liver fibrosis (7).…”

“…The prognostic value of hub genes was verified on the UALCAN data analysis platform, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of hub genes in distinguishing HCC tissues (HBV-HCC and HCV-HCC) from normal liver tissues. Transcription factor and m 6 A methylation predictions were performed using hTFtarget and m6A2Target and validated in microarrays for hub gene. Therapeutic drugs related to genes were explored and developed by STITCH, and effect intensity analysis was performed on computer simulation software (Schrodinger).…”

HPV E6 upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer

“…Forexample, DNA viruses such as adenovirus encode viral proteins that downregulate death receptors and inhibit caspase activation (60). It has been suggested that some of these antiapoptotic functions of the viruses contribute to the oncogenic process during virus-driven cancer progression (60)(61)(62)(63).…”