The association between hepatocarcinogenesis and intracellular alterations due to hepatitis B virus infection

Tsuge, Masataka

doi:10.1111/liv.15065

Cited by 7 publications

(4 citation statements)

References 151 publications

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“…PI3K/AKT/ MTOR pathways [40][41][42]. Of clinical relevance, hepatitis B virus (HBV) has additional properties to induce liver carcinogenesis, including the action of a viral oncoprotein and the integration of the virus in the human genome [43]. Mutations of p53 are observed in 20-50% of HCC [44,45].…”

Section: Discussionmentioning

confidence: 99%

The p53 Family of Transcription Factors Represses the Alpha- fetoprotein Gene Expression in Hepatocellular Carcinoma

Wölfel,

Ostheim,

Staub

et al. 2023

JGLD

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Background: p53 deletion and mutation as well as upregulation of alpha-fetoprotein (AFP) are hallmarks of hepatocarcinogenesis. p63 and p73 belong to the family of p53-related transcription factors expressing a variety of isoforms. The expression of dominant negative (ΔN) p73 is related to the reduced survival of patients with hepatocellular carcinoma (HCC). In this study, we characterized the interaction between p53 family-dependent signaling pathways and the regulation of AFP at the gene and protein levels as essential determinants of therapeutic response and prognosis in HCC. Methods: Putative p53-, p63- and p73-binding sites within the AFP gene were identified in silico. Hep3B cells were transfected with plasmids encoding for p53, p63 and p73 to analyze the interplay of the p53 family with AFP. AFP transcription was determined by RT-qPCR. Protein levels of AFP, p53, p63 and p73 were analyzed by Western blot. Results: Underlining the importance of the crosstalk between the p53 family-dependent pathways and AFP regulation we identified eight novel putative binding sites for the members of the p53 family within the introns 1, 2, 3, 4, 7, 8, 11, and 12 of the AFP gene. Accordingly, full-length isoforms of p53, p63 and p73 efficiently downregulated AFP both on mRNA and protein level. Thus, the p53 family members were identified to be major regulators of AFP repression. Of note, p63 was characterized as a novel and p73 as the most efficient repressor of AFP. Conclusion: p53 mutation and upregulation of AFP are essential oncogenic events in the development of HCC. Here we show that AFP gene regulation occurs via a combined action of the p53 family members p53, p63 and p73. All three tumor suppressors reduce AFP gene and protein expression. Thus, our findings reveal a novel interaction of p53 family-dependent signaling pathways and AFP regulation at the gene and protein levels in HCC.

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Section: Discussionmentioning

confidence: 99%

The p53 Family of Transcription Factors Represses the Alpha- fetoprotein Gene Expression in Hepatocellular Carcinoma

Wölfel,

Ostheim,

Staub

et al. 2023

JGLD

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“…Hepatitis B core (HBc) protein has crucial contribution in HBV replication and intracellular signalling pathways and responsible for hepatocarcinogenesis in patients with HBV infection. 29 The previous study has demonstrated that HBc can interfere with a number of pathways, such as those involved in cell movement and expansion, programed cell death, cellular metabolism, and immune system function via the generation and creation of cytokines that are proinflammatory. Likewise, by adhering to trigger areas and interfering with the production of host DNA, HBc can alter the typical activity of liver cells.…”

Section: Hbv Core (Hbc) Protein As a Proto-oncogene In Hbv-induced Hccmentioning

confidence: 99%

Histomolecular characterisation of hepatitis B virus induced liver cancer

Adugna

2023

Reviews in Medical Virology

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Hepatitis B virus (HBV)‐associated liver cancer is the third most prevalent cancer‐related cause of death worldwide. Different studies have been done on the histomolecular analysis of HBV induced‐liver cancer including epigenetics which are dynamic molecular mechanisms to control gene expression without altering the host deoxyribonucleic acid, genomics characterise the integration of the viral genome with host genome, proteomics characterise how gene modifies and results overexpression of proteins, glycoproteomics discover different glyco‐biomarker candidates and show glycosylation in malignant hepatocytes, metabolomics characterise how HBV impairs a variety of metabolic functions during hepatocyte immortalisation, exosomes characterise immortalised liver cells in terms of their differentiation and proliferation, and autophagy plays a role in the development of hepatocarcinogenesis linked to HBV infection.

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“…The G1896A stop codon mutation in the preC region results in HBeAg translation stopping prematurely ( Mohebbi et al, 2012 ; Tsuge, 2021 ). A recent study showed that G1896A mutation could promote HCC tumor growth in vivo by enhancing HBV replication and activating of ERK/MAPK pathway ( Zhao et al, 2023 ).…”

Section: Hbv Mutations and Impacts On Hccmentioning

confidence: 99%

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways

Shoraka,

Hosseinian,

Hasibi

et al. 2023

Front. Microbiol.

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Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways.

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The association between hepatocarcinogenesis and intracellular alterations due to hepatitis B virus infection

Cited by 7 publications

References 151 publications

The p53 Family of Transcription Factors Represses the Alpha- fetoprotein Gene Expression in Hepatocellular Carcinoma

The p53 Family of Transcription Factors Represses the Alpha- fetoprotein Gene Expression in Hepatocellular Carcinoma

Histomolecular characterisation of hepatitis B virus induced liver cancer

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways

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