Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma

Zou, Tao; Chen, Yao; Zhao, Yueshui; Wu, Xu; Li, Mingxing; Du, Fukuan; Chen, Yu; Xiao, Zhangang; Shen, Jing

doi:10.1007/s12072-022-10351-6

Cited by 18 publications

(18 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4H), which further confirmed the tumor-promoting effect of RBCK1. Recent evidence has proved that HBx is paramount in regulating multiple cellular processes in HBVassociated HCC, including cell proliferation and migration [6,21,22]. To explore whether RBCK1 participated in regulating the activation of HBx-related signal pathways, we performed Gene set enrichment analysis (GSEA) using the differential expression genes between high RBCK1 expression and low RBCK1 expression group.…”

Section: Resultsmentioning

confidence: 99%

RBCK1 promotes the stabilization of HBx by linear ubiquitination to drive the progression of HBV-associated hepatocellular carcinoma

Chen

Dong

et al. 2023

Preprint

View full text Add to dashboard Cite

Background & Aims: Linear ubiquitin chain assembly complex (LUBAC) has been reported to participate in cancer progression, but its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the functions and potential tumorigenic mechanisms of LUBAC components in HBV-associated HCC. Methods: The expression of LUBAC components ( RBCK1, RNF31, and Sharpin) and Met1-linked ubiquitination (M1-Ubi) and their correlation with prognosis were detected. The biological functions of RBCK1 in HBV-associated HCC were investigated in vitro and in vivo. The regulation of RBCK1 on the HBx protein expression was analyzed by cycloheximide chase assays, coimmunoprecipitation, and ubiquitin assays. Results: We found that the expression of LUBAC components and M1-Ubi was significantly upregulated in HCC and correlated with poor prognosis. Interestingly, subgroup analysis revealed that RBCK1, not RNF31 or Sharpin, was exclusively overexpressed in HBV-associated HCC compared to non-HBV-associated HCC. Upregulated RBCK1 expression was associated with larger tumor size, higher AFP level, and poor prognosis in HBV-associated HCC cohort. Functionally, RBCK1-knockdown suppressed cell growth and migration, and also inhibited the progression of xenografted tumors in HBV-associated HCC mouse model. Mechanistically, RBCK1 interacted with HBx to promote its stabilization by increasing M1-Ubi ubiquitination and reducing K48-linked ubiquitination. Furthermore, clinical analysis confirmed a positive correlation between RBCK1 and HBx, and the co-expression of which predicted poor prognosis for HCC patients. Conclusion: RBCK1 is an oncogenic gene to promote tumor progression and may serve as a potential target for HBV-associated HCC.

show abstract

Section: Resultsmentioning

confidence: 99%

RBCK1 promotes the stabilization of HBx by linear ubiquitination to drive the progression of HBV-associated hepatocellular carcinoma

Chen

Dong

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This viral minichromosome establishes a distinct chromatin state and is decorated predominantly with active transcription-associated histone post-translational modifications (PTMs) ( 7, 10, 11 ). Although the precise details of this process are not fully resolved, so-called “epigenetic” drugs targeting chromatin-modifying factors have emerged as attractive potential therapeutic opportunities in HBV ( 12, 13 ). Presently, long-term treatment with oral nucleos(t)ide analogs or short-term treatment with interferon-alpha injections remains the standard of care to halt viral proliferation, but these fall short of eradicating cccDNA in infected hepatocytes ( 2 ).…”

Section: Main Textmentioning

confidence: 99%

A nucleosome switch primes Hepatitis B Virus infection

Prescott

Mansisidor

Bram

et al. 2023

Preprint

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The first viral protein expressed, HBx, induces degradation of a host silencing factor to facilitate infection. However, the relationship between cccDNA chromatin and early HBx transcription remains poorly understood. Establishing reconstituted viral minichromosomes, we found that nucleosomes in cccDNA drive HBx transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing drug CBL137 inhibits infection in hepatocytes. Our results shed new light on a long-standing paradox and represent a novel therapeutic avenue for the treatment of chronic HBV.One-Sentence SummaryChromatin assembly on the Hepatitis B Virus genome drives transcription of the critical viral oncogene HBx, and thus infection.

show abstract

“…The HBx protein can start epigenetic modifications that dysregulate the expression of miRNA, which in turn can control subsequent epigenetic changes in the pathogenesis of HBV-HCC. [15][16][17] Real-time polymerase chain reaction (RT-PCR) results from earlier studies indicate that miR-132 expression was down-regulated in HCC cells that express HBx compared to control HCC cells. Specifically, it was discovered that HBx-induced DNA methylation of the gene promoter mediates the mechanism by which miR-132 is suppressed.…”

Section: Epigeneticsmentioning

confidence: 99%

Histomolecular characterisation of hepatitis B virus induced liver cancer

Adugna

2023

Reviews in Medical Virology

View full text Add to dashboard Cite

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.

show abstract

Hepatitis B virus X protein mediated epigenetic alterations in the pathogenesis of hepatocellular carcinoma

Cited by 18 publications

References 128 publications

RBCK1 promotes the stabilization of HBx by linear ubiquitination to drive the progression of HBV-associated hepatocellular carcinoma

RBCK1 promotes the stabilization of HBx by linear ubiquitination to drive the progression of HBV-associated hepatocellular carcinoma

A nucleosome switch primes Hepatitis B Virus infection

Histomolecular characterisation of hepatitis B virus induced liver cancer

Contact Info

Product

Resources

About