Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein

Laurson, Joanna; Khan, Sadaf; Chung, Rachel; Cross, KJ; Raj, Kenneth

doi:10.1093/carcin/bgq027

Cited by 153 publications

(135 citation statements)

References 69 publications

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“…Moreover, hypermethylation of various tumor suppressor genes causes their transcriptional silencing and removes a barrier of normal proliferation, which may result in malignant transformation. Most interestingly, overexpression of DNMT1 and DNMT3B has been found to be common in human tumors (14)(15)(16)(17), and this overexpression could also be associated with HPV infections (18)(19)(20) residues. These modifications are mediated by proline hydroxylases (PHDs), whose activity is regulated by O 2 availability (22).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

Łuczak

Roszak²,

Pawlik³

et al. 2011

Int J Oncol

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Abstract. The development of cervical cancer requires genetic and epigenetic factors which result in the persistence of a malignant phenotype. Cervical cancer exhibits also some unique differences from other solid tumors. Normal cervical stratified epithelia have characteristics of hypoxic tissue with over-expression of HIF-1 (hypoxia-inducible factor-1) transcription factor, which targets the transcription of over 70 genes involved in many aspects of cancer biology. One of the genes, which could be induced by HIF-1 is chemokine (C-X-C motif) receptor 4 (CXCR4). CXCR4 could also be epigenetically regulated by methylation of CpG dinucleotides located in the promoter region. Here, we examined the CXCR4, DNMT3A, DNMT3B and DNMT1 transcript levels in cancer tissue (n=30) and non-cancer, normal uterine cervical tissue (n=30) from a Polish cohort. We also compared the methylation status of CXCR4 promoter region in cancer and normal tissue samples. Our result showed significantly higher levels of CXCR4, DNMT3A, DNMT3B and DNMT1 transcript (p=0.0058, 0.0163, 0.0003 and <0.0001, respectively) levels in cancer tissue as compared to normal samples. We did not observe DNA methylation in the CXCR4 promoter region in either control or cancer tissue samples. CXCR4 has a functional hypoxia response element (HRE) in the promoter region, located -1.3 kb from the transcription start site. Our work shows for the first time that HIF-1A could promote the induction of CXCR4 gene expression (Spearman's correlation coefficient = 0.515, p=0.003) in patients with primary advanced

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Section: Introductionmentioning

confidence: 99%

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

Łuczak

Roszak²,

Pawlik³

et al. 2011

Int J Oncol

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“…For example, the hepatitis B virus X protein upregulates DNMT1 and DNMT3A but downregulates DNMT3B, the hepatitis C virus core protein upregulates DNMT1 and DNMT3B, human papillomavirus E7 and adenovirus E1A upregulate DNMT1, and Kaposi's sarcoma-associated herpesvirus LANA protein upregulates DNMT3A (2,6,18,24,30,31,40). The major Epstein-Barr virus (EBV) oncogene, the latent membrane protein 1 (LMP1) gene, upregulates DNMT1, DNMT3A, and DNMT3B in nasopharyngeal carcinoma cell lines and has been shown to induce methylation of the tumor suppressor genes, the RARB and CDH13 genes, in these lines (30,35).…”

mentioning

confidence: 99%

Epigenetic and Transcriptional Changes Which Follow Epstein-Barr Virus Infection of Germinal Center B Cells and Their Relevance to the Pathogenesis of Hodgkin's Lymphoma

Leonard

Wei

Anderton

et al. 2011

J Virol

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Although Epstein-Barr virus (EBV) usually establishes an asymptomatic lifelong infection, it is also implicated in the development of germinal center (GC) B-cell-derived malignancies, including Hodgkin's lymphoma (HL). Following primary infection, EBV remains latent in the memory B-cell population, where host-driven methylation of viral DNA contributes to the repression of viral gene expression. However, it is still unclear how EBV harnesses the cell's methylation machinery in B cells, how this contributes to viral persistence, and what impact this has on the methylation of cellular genes. We show that EBV infection of GC B cells is followed by upregulation of the DNA methyltransferase DNMT3A and downregulation of DNMT3B and DNMT1. We show that the EBV latent membrane protein 1 (LMP1) oncogene downregulates DNMT1 and that DNMT3A binds to the viral promoter Wp. Genome-wide promoter arrays performed with these cells showed that EBVassociated methylation changes in cellular genes were not randomly distributed across the genome but clustered at chromosomal locations, consistent with an instructive pattern of methylation, and were in part determined by promoter CpG content. Both DNMT3B and DNMT1 were downregulated and DNMT3A was upregulated in HL cell lines, recapitulating the pattern of expression observed following EBV infection of GC B cells. We also found, by using gene expression profiling, that genes differentially expressed following EBV infection of GC B cells were significantly enriched for those reported to be differentially expressed in HL. These observations suggest that EBV-infected GC B cells are a useful model for studying virus-associated changes contributing to the pathogenesis of HL.

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“…These cells develop virus induced chromosome damage and can undergo abnormal mitosis (Table 2), both in vitro and [64] E6, E7 [66,67] Naturally occurring pre-S mutants [68] --EBNA-3C v-CYC [65] LMP-1 [63] Lytic proteins BZLF-1 [69] -E1, E2 [71,72] HBx [73,74] Core Tax [76,77] BGLF-5 [70] NS3 [23,62] NS5 [75] EBV: Epstein-Barr virus; HHV-8: Human herpesvirus 8, also named Kaposi sarcoma virus; HPV: Human papillomavirus; HBV: Hepatatis B virus; HCV: Hepatitis C virus; HTLV-1: Human T-cell leukemia virus 1. EBNA-3A, EBNA-3C [78] LANA-1 [81] E6 [83] HBx [85,86] Core [87] Tax [88] LMP-1 [79] microRNA [82] E7 [84] LMP-2 [80] EBV: Epstein-Barr virus; HHV-8: Human herpesvirus 8, also named Kaposi sarcoma virus; HPV: Human papillomavirus; HBV: Hepatatis B virus; HCV: Hepatitis C virus; HTLV-1: Human T-cell leukemia virus 1.…”

Section: A Mechanism For Tumor Initiation In Viral Persistencementioning

confidence: 99%

How virus persistence can initiate the tumorigenesis process

Avanzi

Alvisi²,

Ripalti³

2013

WJV

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Human oncogenic viruses are defined as necessary but not sufficient to initiate cancer. Experimental evidence suggests that the oncogenic potential of a virus is effective in cells that have already accumulated a number of genetic mutations leading to cell cycle deregulation. Current models for viral driven oncogenesis cannot explain why tumor development in carriers of tumorigenic viruses is a very rare event, occurring decades after virus infection. Considering that viruses are mutagenic agents per se and human oncogenic viruses additionally establish latent and persistent infections, we attempt here to provide a general mechanism of tumor initiation both for RNA and DNA viruses, suggesting viruses could be both necessary and sufficient in triggering human tumorigenesis initiation. Upon reviewing emerging evidence on the ability of viruses to induce DNA damage while subverting the DNA damage response and inducing epigenetic disturbance in the infected cell, we hypothesize a general, albeit inefficient hit and rest mechanism by which viruses may produce a limited reservoir of cells harboring permanent damage that would be initiated when the virus first hits the cell, before latency is established. Cells surviving virus generated damage would consequently become more sensitive to further damage mediated by the otherwise insufficient transforming activity of virus products expressed in latency, or upon episodic reactivations (viral persistence). Cells with a combination of genetic and epigenetic damage leading to a cancerous phenotype would emerge very rarely, as the probability of such an occurrence would be dependent on severity and frequency of consecutive hit and rest cycles due to viral reinfections and reactivations

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Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein

Cited by 153 publications

References 69 publications

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma

Epigenetic and Transcriptional Changes Which Follow Epstein-Barr Virus Infection of Germinal Center B Cells and Their Relevance to the Pathogenesis of Hodgkin's Lymphoma

How virus persistence can initiate the tumorigenesis process

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