Hepatitis B virus X protein and TGF-β: partners in the carcinogenic journey of hepatocellular carcinoma

• Published in: Frontiers in oncology Vol. 14; p. 1407434
• Main Authors: Yan, Wei, Rao, Dean, Fan, Feimu, Liang, Huifang, Zhang, Zunyi, Dong, Hanhua
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.06.2024
• Subjects: HBx protein; hepatitis B virus; hepatocellular carcinoma; Oncology; pro-tumorigenic; TGF-β signaling; tumor suppressor; pro-tumorigenic; tumor suppressor; TGF-β signaling; hepatitis B virus; HBx protein; hepatocellular carcinoma
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2024.1407434

Hepatitis B infection is substantially associated with the development of liver cancer globally, with the prevalence of hepatocellular carcinoma (HCC) cases exceeding 50%. Hepatitis B virus (HBV) encodes the Hepatitis B virus X (HBx) protein, a pleiotropic regulatory protein necessary for the transcription of the HBV covalently closed circular DNA (cccDNA) microchromosome. In previous studies, HBV-associated HCC was revealed to be affected by HBx in multiple signaling pathways, resulting in genetic mutations and epigenetic modifications in proto-oncogenes and tumor suppressor genes. In addition, transforming growth factor-β (TGF-β) has dichotomous potentials at various phases of malignancy as it is a crucial signaling pathway that regulates multiple cellular and physiological processes. In early HCC, TGF-β has a significant antitumor effect, whereas in advanced HCC, it promotes malignant progression. TGF-β interacts with the HBx protein in HCC, regulating the pathogenesis of HCC. This review summarizes the respective and combined functions of HBx and TGB-β in HCC occurrence and development.