The role of Epstein–Barr virus in nasopharyngeal carcinoma

Su, Z.; Siak, Pui Yan; Leong, Chee‐Onn; Cheah, Shiau‐Chuen

doi:10.3389/fmicb.2023.1116143

Cited by 37 publications

(29 citation statements)

References 201 publications

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“…While latent EBV infection of naïve B-lymphocytes causes B-cell activation, leading to B-cell blasts [1,2], intermittent lytic cycle reactivation is important for production of viral progeny as well as transmission from one host to another [54]. Accumulating evidence suggests the involvement of viral lytic cycle replication in EBV associated cancers, particularly in case of nasopharyngeal carcinoma [90]. In addition, by incompletely characterized mechanisms differentiation of B-cells into plasma cells was shown to promote EBV lytic cycle replication [55].…”

Section: Discussionmentioning

confidence: 99%

Differential Carbonic Anhydrase Activities Control EBV-Induced B-Cell Transformation and Lytic Cycle Reactivation

Malik,

Biswas,

Sarkar

et al. 2023

Preprint

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Epstein-Barr virus (EBV) contributes to ∼1% of all human cancers including several B-cell neoplasms. A characteristic feature of EBV life cycle is its ability to transform metabolically quiescent B-lymphocytes into hyperproliferating B-cell blasts with the establishment of viral latency, while intermittent lytic cycle induction is necessary for the production of progeny virus. Our RNA-Seq analyses of both latently infected naïve B-lymphocytes and transformed B-lymphocytes upon lytic cycle replication indicate a contrasting expression pattern of a membrane-associated carbonic anhydrase isoform CA9, an essential component for maintaining cell acid-base homeostasis. We show that while CA9 expression is transcriptionally activated during latent infection model, lytic cycle replication restrains its expression. Pharmacological inhibition of CA-activity using specific inhibitors retards EBV induced B-cell transformation, inhibits B-cells outgrowth and colony formation ability of transformed B-lymphocytes through lowering the intracellular pH, induction of cell apoptosis and facilitating degradation of CA9 transcripts. Reanalyses of ChIP-Seq data along with utilization of EBNA2 knockout virus and sh-RNA mediated knockdown of CA9 expression we further demonstrate that EBNA2 mediated CA9 transcriptional activation is essential for EBV latently infected B-cell survival. In contrast, during lytic cycle reactivation CA9 expression is transcriptionally suppressed by the key EBV lytic cycle transactivator, BZLF1 through its transactivation domain. Overall, our study highlights the dynamic alterations of CA9 expression and its activity in regulating pH homeostasis act as one of the major drivers for EBV induced B-cell transformation and subsequent B-cell lymphomagenesis.

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Section: Discussionmentioning

confidence: 99%

Differential Carbonic Anhydrase Activities Control EBV-Induced B-Cell Transformation and Lytic Cycle Reactivation

Malik,

Biswas,

Sarkar

et al. 2023

Preprint

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“…The presence of EBV DNA or transcripts in tumour cells and clonal EBV genomes in NPC and precancerous lesions further solidified the relationship between EBV and NPC 102 . Non‐keratinising carcinomas, the primary subtype of NPC, are strongly associated with EBV infection 103 . The expression of circRNAs in NPCs significantly differs from that in normal tissues, suggesting that circRNAs play a vital role in NPC development and progression 104,105 …”

Section: Roles Of Cerna Network and Virus‐related Cancersmentioning

confidence: 96%

“…102 Non-keratinising carcinomas, the primary subtype of NPC, are strongly associated with EBV infection. 103 The expression of circRNAs in NPCs significantly differs from that in normal tissues, suggesting that circRNAs play a vital role in NPC development and progression. 104,105 The findings of Lin et al suggest significant differences in the expression of the circRNA/miRNA/mRNA axis between EBV-positive and EBV-negative cells.…”

Section: Nasopharyngeal Carcinomamentioning

confidence: 99%

Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers

Kamali,

Salehi,

Mostafavi

et al. 2024

Reviews in Medical Virology

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A significant portion of human cancers are caused by oncoviruses (12%–25%). Oncoviruses employ various strategies to promote their replication and induce tumourigenesis in host cells, one of which involves modifying the gene expression patterns of the host cells, leading to the rewiring of genes and resulting in significant changes in cellular processes and signalling pathways. In recent studies, a specific mode of gene regulation known as circular RNA (circRNA)‐mediated competing endogenous RNA (ceRNA) networks has emerged as a key player in this context. CircRNAs, a class of non‐coding RNA molecules, can interact with other RNA molecules, such as mRNAs and microRNAs (miRNAs), through a process known as ceRNA crosstalk. This interaction occurs when circRNAs, acting as sponges, sequester miRNAs, thereby preventing them from binding to their target mRNAs and modulating their expression. By rewiring the host cell genome, oncoviruses have the ability to manipulate the expression and activity of circRNAs, thereby influencing the ceRNA networks that can profoundly impact cellular processes such as cell proliferation, differentiation, apoptosis, and immune responses. This review focuses on a comprehensive evaluation of the latest findings on the involvement of virus‐induced reprogramming of host circRNA‐mediated ceRNA networks in the development and pathophysiology of human viral cancers, including cervical cancer, gastric cancer, nasopharyngeal carcinoma, Kaposi's sarcoma, hepatocellular carcinoma, and diffuse large B cell lymphoma. Understanding these mechanisms can improve our knowledge of how oncoviruses contribute to human tumourigenesis and identify potential targets for developing optimised therapies and diagnostic tools for viral cancers.

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“…NPC is an Epstein–Barr virus (EBV)‐related malignancy, given that clonotypic EBV genomes and EBV oncogenic proteins are detected in most NPC patients in endemic areas such as southern China 1 . Furthermore, many reports to date have shown an important association between persistent EBV infection and EBV gene products and tumor initiation, promotion, and progression in NPC 1–3 . With regard to the histological characteristics of NPC, many immunocompetent cells infiltrate the tumor stroma, including lymphocytes, granulocytes, and macrophages, 4 suggesting that interactions between tumor cells and infiltrating immune cells via cell surface molecules may be an important contributor to malignancy.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD27 as a predictive biomarker for intra‐tumoral CD70/CD27 interaction in nasopharyngeal carcinoma

Nagato,

Komatsuda,

Hayashi

et al. 2024

Cancer Science

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In CD70‐expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)‐related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27‐positive lymphocytes infiltrate around tumor cells. NPC patients with CD27‐positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27‐positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70‐positive NPC with CD27‐positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27‐targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.

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The role of Epstein–Barr virus in nasopharyngeal carcinoma

Cited by 37 publications

References 201 publications

Differential Carbonic Anhydrase Activities Control EBV-Induced B-Cell Transformation and Lytic Cycle Reactivation

Differential Carbonic Anhydrase Activities Control EBV-Induced B-Cell Transformation and Lytic Cycle Reactivation

Hijacking and rewiring of host CircRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) regulatory networks by oncoviruses during development of viral cancers

Soluble CD27 as a predictive biomarker for intra‐tumoral CD70/CD27 interaction in nasopharyngeal carcinoma

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