Hepatitis B virus integration and hepatocarcinogenesis

Abstract

Hepatitis B virus (HBV) is the most common cause of hepatocellular carcinoma (HCC), which is the predominant liver cancer type in Southeast Asia. Approximately 350 million individuals suffer from persistent hepatitis B infection worldwide. HBV promotes HCC development through direct and indirect mechanisms. HBV DNA integrates into the host genome during the initial stages of tumorigenesis, causing insertional mutagenesis of cancer-related genes and genomic instability. Extrachromosomal circular DNA (ecDNA) is formed, which is efficiently amplified in large quantities to express viral genes and host oncogenes. Moreover, virus-associated proteins, such as the regulatory HBV X (HBx) protein and/or the modified preS/S envelope protein, alter the expression of genes associated with multiple functions in host cells. In this review, we summarize the role of the HBx and preS/S proteins in promoting tumorigenesis. In addition to summarizing the specific mechanism of HBV-related tumorigenesis, the concerns and perspectives for future study are discussed.

Keywords

Hepatocellular carcinoma (HCC) / Extrachromosomal circular DNA (ecDNA) / Hepatitis B virus X (HBx) protein / Hepatocarcinogenesis

Authors’ contributions

Linlin Ma: Writing - review & editing, Writing - original draft, Visualization. Shuzhen Chen: Writing - review & editing, Writing - original draft, Funding acquisition. Hongyang Wang: Concep-tualization, Supervision, Project administration, Writing - review & editing, Funding acquisition. Lei Chen: Conceptualization, Su-pervision, Project administration, Writing - review & editing, Funding acquisition.

Declaration of competing interest

The authors declare that there is no conflict of interest.

Acknowledgements

This work was supported by the National Natural Science Foun-dation of China (grant numbers: 81988101, 82173146, U21A20376, 82425038, and 82421005), the Natural Science Foundation of Shanghai (grant numbers: 22140901000 and 21XD1404600), and the National Key R&D Program of China (grant numbers: 2023YFC2507500).

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