Nasopharyngeal Carcinoma: An Evolving Role for the Epstein–Barr Virus

Abstract

The Epstein-Barr herpesvirus (EBV) is an important human pathogen that is closely linked to several major malignancies including the major epithelial tumor, undifferentiated nasopharyngeal carcinoma (NPC). This important tumor occurs with elevated incidence in specific areas, particularly in southern China but also in Mediterranean Africa and some regions of the Middle East. Regardless of tumor prevalence, undifferentiated NPC is consistently associated with EBV. The consistent detection of EBV in all cases of NPC, the maintenance of the viral genome in every cell, and the continued expression of viral gene products suggest that EBV is a necessary factor for the malignant growth in vivo. However, the molecular characterization of the infection and identification of critical events have been hampered by the difficulty in developing in vitro models of NPC. Epithelial cell infection is difficult in vitro and in contrast to B-cell infection does not result in immortalization and transformation. Cell lines established from NPC usually do not retain the genome, and the successful establishment of tumor xenografts is difficult. However, critical genetic changes that contribute to the onset and progression of NPC and key molecular properties of the viral genes expressed in NPC have been identified. In some cases, viral expression becomes increasingly restricted during tumor progression and tumor cells may express only the viral nuclear antigen EBNA1 and viral noncoding RNAs. As NPC develops in the immunocompetent, the continued progression of deregulated growth likely reflects the combination of expression of viral oncogenes in some cells and viral noncoding RNAs that likely function synergistically with changes in cellular RNA and miRNA expression.

Serum long non-coding RNAs MALAT1, AFAP1-AS1 and AL359062 as diagnostic and prognostic biomarkers for nasopharyngeal carcinoma

“…Persistently latent EBV infection has been found among the majority of NPC patients, indicating its etiological role in initiation and progression of NPC [26–28]. Here, we found levels of MALAT1, AFAP1-AS1 and AL359062 significantly increased in NP69 cell after EBV infection.…”

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

“…Establishement of EBV latent infection has been considered as an early event in NPC development, because of EBV infection was observed in premalignant lesions of the nasopharynx (Pathmanathan, Prasad, Sadler, Flynn, & Raab‐Traub, ). However, unlike to B‐cell infection, in vitro EBV infection of epithelial cells fail to immortalization and transformation (Raab‐Traub, ), which argue it's initiating role in NPC oncogenesis. It has been shown forced expression of telomerase reverse transcriptase (hTERT) led to immortalization of NPE cells.…”

Dissecting the regulation of EBV's BART miRNAs in carcinomas

“…Infection with EBV is associated with several human cancers, including Burkitt’s lymphoma (BL), Hodgkin’s disease, post-transplant lymphoproliferative disease, and both gastric and nasopharyngeal carcinoma (NPC) (Brady et al, 2007; Hammerschmidt and Sugden, 2004; Raab-Traub, 2002, 2015; Sugden, 2014; Tse and Kwong, 2015). This tumor virus infects quiescent B cells, induces their proliferation, and is maintained in them in a latent state where its genome exists as a circular plasmid.…”