Epigenetic changes in virus-associated human cancers

Li, Hsin Pai; Leu, Yu Wei; Chang, Yu‐Sun

doi:10.1038/sj.cr.7290295

Cited by 84 publications

(79 citation statements)

References 86 publications

(85 reference statements)

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“…DNA methylation is one of the strategies that some viruses use to avoid detection by the immune system (Butel, 2000;Verma et al, 2007); specifically, the deregulation of DNMT family members has been proposed as one of the mechanisms that modulate gene expression in these interactions (Li et al, 2005). Therapy with demethylating agents in this kind of pathology has not yet been used against solid tumors in vivo, but for example, DNMT3B inhibitors could potentially be useful in HCC (Park et al, 2007a).…”

Section: Discussionmentioning

confidence: 99%

“…T antigens are largely responsible for these alterations, and may interact with HATs (p300 and CBP) to enhance or repress gene expression (DeCaprio, 2009), or may induce aberrant methylation, possibly mediated by DNMTs (McCabe et al, 2006), in host gene promoters in several tumor types (Li et al, 2005;Goel et al, 2006).…”

Section: Polyomaviruses: Sv40 Jcv Bkv and MCVmentioning

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: Discussionmentioning

confidence: 99%

Section: Polyomaviruses: Sv40 Jcv Bkv and MCVmentioning

confidence: 99%

Viral epigenomes in human tumorigenesis

Fernández

Esteller

2010

Oncogene

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“…Apart from introducing genetic changes, the presence of some oncogenic viruses was found to be correlated with the aberrant methylation profile of multiple TSGs in human cancers. 61,62 It is nowadays likely that SV40 may activate an aberrant methylation pathway that affects multiples TSGs during lymphomagenesis; however, the molecular mechanism underlying SV40-related aberrant methylation is currently still unknown. Determining precisely how SV40 infection leads to aberrant hypermethylation of promoter genes in human cancers seems to be a key question to be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Presence of simian virus 40 DNA sequences in diffuse large B‐cell lymphomas in Tunisia correlates with aberrant promoter hypermethylation of multiple tumor suppressor genes

Amara

Trimèche

Ziadi

et al. 2007

Intl Journal of Cancer

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The simian virus SV40 (SV40), a potent DNA oncogenic polyomavirus, has been detected in several human tumors including lymphomas, mainly in diffuse large B-cell type (DLBCL). However, a causative role for this virus has not been convincingly established. Hypermethylation in promoter regions is a frequent process of silencing tumor suppressor genes (TSGs) in cancers, which may be induced by oncogenic viruses. In this study, we investigated the relationship between the presence of SV40 DNA sequences and the methylation status of 13 TSGs in 108 DLBCLs and 60 nontumoral samples from Tunisia. SV40 DNA presence was investigated by PCR assays targeting the large T-antigen, the regulatory and the VP1 regions. Hypermethylation was carried out by methylationspecific PCR. SV40 DNA was detected in 63/108 (56%) of DLBCL and in 4/60 (6%) of nontumoral samples. Hypermethylation frequencies for the tested TSGs were 74% for DAPK, 70% for CDH1, SHP1, and GSTP1, 58% for p16, 54% for APC, 50% for p14, 39% for p15, 19% for RB1, 15% for BLU, 3% for p53, and 0% for p300 and MGMT. No hypermethylation was observed in nontumoral samples. Hypermethylation of SHP1, DAPK, CDH1, GSTP1 and p16 genes were significantly higher in SV40-positive than in SV40-negative DLBCL samples (p values ranging from 0.0006 to <0.0001). Our findings showed a high prevalence of SV40 DNA in DLBCLs in Tunisia. The significant association of promoter hypermethylation of multiple TSGs with the presence of SV40 DNA in DLBCLs supports a functional effect of the virus in those lymphomas. ' 2007 Wiley-Liss, Inc.Key words: diffuse large B-cell lymphomas; simian virus 40; hypermethylation; tumor suppressor genes; Tunisia Simian virus 40 (SV40) is a potent DNA oncogenic polyomavirus of rhesus monkey origin which seems to have spread to human beings via contamination of poliovirus stocks between 1955 and 1963 as well as by other means, 1 and mounting evidence suggests that it is an emergent human pathogen. 2-4 SV40 DNA sequences have been detected in pediatric and adult brain tumors, 5,6 mesotheliomas, 7 osteosarcomas, 8 bronchopulmonary carcinomas, 9 bone tumors 10 and papillary thyroid carcinomas. 11 There also increasing evidence that SV40 is associated with non-Hodgkin's lymphomas, particularly with diffuse large B-cell lymphomas (DLBCL), 12-21 in spite of several negative studies. [22][23][24] However, although these observations indicate an association between this virus and specific human tumors, they do not demonstrate a causal role, and the molecular mechanism by which SV40 thought to be involved is still unclear.SV40 oncogenic potential is assumed to be associated with the primary viral gene product, large T-antigen (Tag), protein responsible for SV40 replication and SV40-mediated cell transformation. 1 In vitro, the infection of human cells by SV40 has showed that SV40 Tag can promote malignancy transformation by blocking the products of several tumor suppressor genes (TSGs), 1,25 inducing telomerase activity, 26 and stimulating other oncogenes and growth facto...

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“…One hundred and forty-two miRNAs were identified as differentially expressed in JFH-1 HCV-infected and UV-inactivated HCV-infected Huh7.5.1 cells. Increased levels of miR-181a, miR-210 and miR-221 were observed in JFH1-infected Huh7.5.1 cells; and miR-455-3p slightly suppressed HCV propagation in vitro; as compared to UV-inactivated control cells [71]. Virus entry assays demonstrated that overexpression of miR-923 or inhibition of miR-149*, miR-373*, miR-638, miR-888, miR-940, miR-1181 or miR-1234 enabled entry of HCV pseudoparticles.…”

Section: Roles Of Mirnas In Virus-induced Hccmentioning

confidence: 96%

The role and clinical implications of microRNAs in hepatocellular carcinoma

Zhao

Yang

et al. 2012

Sci. China Life Sci.

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Hepatocellular carcinoma (HCC) is common and one of the most aggressive of all human cancers. Recent studies have indicated that miRNAs, a class of small noncoding RNAs that regulate gene expression post-transcriptionally, directly contribute to HCC by targeting many critical regulatory genes. Several miRNAs are involved in hepatitis B or hepatitis C virus replication and virus-induced changes, whereas others participate in multiple intracellular signaling pathways that modulate apoptosis, cell cycle checkpoints, and growth-factor-stimulated responses. When disturbed, these pathways appear to result in malignant transformation and ultimately HCC development. Recently, miRNAs circulating in the blood have acted as possible early diagnostic markers for HCC. These miRNA also could serve as indicators with respect to drug efficacy and be prognostic in HCC patients. Such biomarkers would assist stratification of HCC patients and help direct personalized therapy. Here, we summarize recent advances regarding the role of miRNAs in HCC development and progression. Our expectation is that these and ongoing studies will contribute to the understanding of the multiple roles of these small noncoding RNAs in liver tumorigenesis.

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Epigenetic changes in virus-associated human cancers

Cited by 84 publications

References 86 publications

Viral epigenomes in human tumorigenesis

Viral epigenomes in human tumorigenesis

Presence of simian virus 40 DNA sequences in diffuse large B‐cell lymphomas in Tunisia correlates with aberrant promoter hypermethylation of multiple tumor suppressor genes

The role and clinical implications of microRNAs in hepatocellular carcinoma

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