Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A

Zheng, Dali; Zhang, Li; Cheng, Na; Xu, Xinlin; Deng, Qing; Teng, Xiao Mei; Wang, Ke Sheng; Zhang, Xin; Huang, Jian; Han, Ze‐Guang

doi:10.1016/j.jhep.2008.10.019

Cited by 169 publications

(168 citation statements)

References 43 publications

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“…In the case of HBV, chronic inflammation and accumulation of genetic alterations in infected hepatocytes induced by the host (Cougot et al, 2005;Gurtsevitch, 2008) and epigenetic alterations produced by viral proteins (Tischoff and Tannapfe, 2008;Herceg and Paliwal, 2009;Shon et al, 2009;Zheng et al, 2009) are mainly responsible for the carcinogenesis induced by HBV.…”

Section: Hepatitis B Virusmentioning

confidence: 99%

“…It has also been proposed that HBV infection induces epigenetic alterations in host cells (Cougot et al, 2007;Jung et al, 2007;Park et al, 2007a;Herceg and Paliwal, 2009;Shon et al, 2009;Zheng et al, 2009). In such a context, HBx is a key factor initiating epigenetic alterations induced by this virus.…”

Section: Hepatitis B Virusmentioning

confidence: 99%

“…In such a context, HBx is a key factor initiating epigenetic alterations induced by this virus. HBx interacts with DNMTs to produce alterations in the expression of key genes through methylation of their promoters (Jung et al, 2007;Park et al, 2007a;Zheng et al, 2009). DNMT1 expression can be activated by HBx and this increase can then inhibit the expression of tumorsuppressor genes such as p16 or E-cadherin (Jung et al, 2007).…”

Section: Hepatitis B Virusmentioning

confidence: 99%

“…DNMT1 expression can be activated by HBx and this increase can then inhibit the expression of tumorsuppressor genes such as p16 or E-cadherin (Jung et al, 2007). HBx can also regulate the expression of DNMT3a and DNMT3b or interact directly with them, resulting in the hypermethylation or hypomethylation of the promoter regions modulating gene expression (Park et al, 2007a;Zheng et al, 2009). In addition, interactions are known to occur between HBx and the chromatin remodeling machinery components (Cougot Interactions between HBx and histone acetyltransferase (HAT) CBP/p300 are associated with the modulation of gene expression (Cougot et al, 2007), and those with histone deacetylase 1 (HDAC1) have been associated with gene repression (Shon et al, 2009;Zheng et al, 2009).…”

Section: Hepatitis B Virusmentioning

confidence: 99%

“…HBx can also regulate the expression of DNMT3a and DNMT3b or interact directly with them, resulting in the hypermethylation or hypomethylation of the promoter regions modulating gene expression (Park et al, 2007a;Zheng et al, 2009). In addition, interactions are known to occur between HBx and the chromatin remodeling machinery components (Cougot Interactions between HBx and histone acetyltransferase (HAT) CBP/p300 are associated with the modulation of gene expression (Cougot et al, 2007), and those with histone deacetylase 1 (HDAC1) have been associated with gene repression (Shon et al, 2009;Zheng et al, 2009). In a recent review, Zdenko Herceg and Anupam Paliwal proposed three hypothetical models that combined the interactions between HBx and the various epigenetic factors to explain the gene expression modulation induced by the virus (Herceg and Paliwal, 2009).…”

Section: Hepatitis B Virusmentioning

confidence: 99%

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Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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Viruses are associated with 15-20% of human cancers worldwide. In the last century, many studies were directed towards elucidating the molecular mechanisms and genetic alterations by which viruses cause cancer. The importance of epigenetics in the regulation of gene expression has prompted the investigation of virus and host interactions not only at the genetic level but also at the epigenetic level. In this study, we summarize the published epigenetic information relating to the genomes of viruses directly or indirectly associated with the establishment of tumorigenic processes. We also review aspects such as viral replication and latency associated with epigenetic changes and summarize what is known about epigenetic alterations in host genomes and the implications of these for the tumoral process. The advances made in characterizing epigenetic features in cancer-causing viruses have improved our understanding of their functional mechanisms. Knowledge of the epigenetic changes that occur in the genome of these viruses should provide us with markers for following cancer progression, as well as new tools for cancer therapy.

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Section: Hepatitis B Virusmentioning

confidence: 99%

Section: Hepatitis B Virusmentioning

confidence: 99%

Section: Hepatitis B Virusmentioning

confidence: 99%

Section: Hepatitis B Virusmentioning

confidence: 99%

Section: Hepatitis B Virusmentioning

confidence: 99%

See 3 more Smart Citations

Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises

El-Araby

Fouad

Hanbal

et al. 2016

Archiv der Pharmazie

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Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed.

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Dual epigenetic changes in diabetes mellitus‐associated pancreatic ductal adenocarcinoma correlate with downregulation of E‐cadherin and worsened prognosis

Hara

Mizukami

Yamazaki

et al. 2023

The Journal of Pathology CR

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Diabetes mellitus (DM) is a risk factor for pancreatic ductal adenocarcinoma (PDAC) that promotes the promoter methylation of CDH1. It is still unclear whether DM can exert other epigenetic effects, such as altering microRNA (miR) expression, in PDAC. The expression of miR‐100‐5p is known to be changed in DM patients and can suppress the expression of E‐cadherin. In this study, the correlation between DM status and dual epigenetic changes was evaluated in PDAC specimens from patients who underwent radical surgical resection. A total of 132 consecutive patients with PDAC were clinicopathologically evaluated. E‐cadherin and nuclear β‐catenin expression was measured using immunohistochemistry. DNA and miRs were extracted from the main tumor site on formalin‐fixed paraffin‐embedded tissue sections. TaqMan miR assays were applied to assess miR‐100‐5p expression. Bisulfite modification was conducted on the extracted DNA, which was then subjected to methylation‐specific polymerase chain reaction. Immunohistochemistry revealed that decreased E‐cadherin expression and increased nuclear β‐catenin expression were significantly associated with DM and poor tumor cell differentiation. The presence of long‐duration DM (≥3 years) was a significant factor contributing to CDH1 promoter methylation (p < 0.01), while miR‐100‐5p expression was proportionally correlated with the preoperative HbA1c level (R = 0.34, p < 0.01), but not the duration of DM. The subjects with high miR‐100‐5p expression and CDH1 promoter methylation showed the highest level of vessel invasion and prevalence of tumor size ≥30 mm. PDAC subjects with dual epigenetic changes showed poorer overall survival (OS) than those with a single epigenetic change. miR‐100‐5p expression ≥4.13 and CDH1 promoter methylation independently predicted poor OS and disease‐free survival (DFS) in the multivariate analysis. OS and DFS worsened in DM subjects with both HbA1c ≥ 6.5% and DM duration ≥3 years. Thus, DM is associated with two modes of epigenetic change by independent mechanisms and worsens prognosis.

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Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A

Cited by 169 publications

References 43 publications

Viral epigenomes in human tumorigenesis

Viral epigenomes in human tumorigenesis

Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises

Dual epigenetic changes in diabetes mellitus‐associated pancreatic ductal adenocarcinoma correlate with downregulation of E‐cadherin and worsened prognosis

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