Investigating the influence of Epstein-Barr virus on the p53 pathway in nasopharyngeal carcinoma

Abstract

Abstract Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelial lining of nasopharynx. It is one of the most common malignancies in the southern area of China and South-East Asia. NPC is frequently reported in Sarawak, Malaysia especially in males and is endemic to certain ethnic groups, including the Bidayuh and Chinese. The development of NPC is associated with multiple factors, with one common mechanism involving persistent infection with Epstein-Barr virus (EBV). This study will aim to gain a clearer understanding regarding the mechanism of EBV influencing p53 pathway to facilitate NPC development. Mutations in p53 mutation have been associated with oncogenesis of several human malignancies, however such mutations are relatively rare in NPC and the mechanisms through which p53 in inactivated in this malignancy remain poorly understood. In this study, we study the activity of p53 in immortalised nasopharyngeal epithelial cells using nutlin-3, an MDM2 antagonist. The impact of EBV infection on the protein expression of p53 and its ability to stimulate its transcriptional target genes is studied. The proteins levels of p53 and its transcriptional activation of target genes was significantly higher in EBV-infected cells, indicating that EBV infection alone is not sufficient to attenuate the p53 pathway in a non-malignant nasopharyngeal cell line. These observations will provide the fundamental steps towards the understanding of p53 and EBV viral proteins interaction that causes NPC. A post-publication change was made to this article on 11 Jun 2020 to correct an author name.