Radio-Susceptibility of Nasopharyngeal Carcinoma: Focus on Epstein- Barr Virus, MicroRNAs, Long Non-Coding RNAs and Circular RNAs

2020 ◽  
Vol 13 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Fanghong Lei ◽  
Tongda Lei ◽  
Yun Huang ◽  
Mingxiu Yang ◽  
Mingchu Liao ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Regulatory Networks ◽  
Epstein Barr Virus ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Circular Rnas ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.

scholarly journals Competitive Endogenous RNA Landscape in Epstein-Barr Virus Associated Nasopharyngeal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiandong Lin ◽  
Steven Wang ◽  
Keyu Lin ◽  
Jingfeng Zong ◽  
Qianlan Zheng ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Differential Expression Analysis ◽  
Target Prediction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Epithelial Cell Line ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

Non-coding RNAs have been shown to play important regulatory roles, notably in cancer development. In this study, we investigated the role of microRNAs and circular RNAs in Nasopharyngeal Carcinoma (NPC) by constructing a circRNA-miRNA-mRNA co-expression network and performing differential expression analysis on mRNAs, miRNAs, and circRNAs. Specifically, the Epstein-Barr virus (EBV) infection has been found to be an important risk factor for NPC, and potential pathological differences may exist for EBV+ and EBV- subtypes of NPC. By comparing the expression profile of non-cancerous immortalized nasopharyngeal epithelial cell line and NPC cell lines, we identified differentially expressed coding and non-coding RNAs across three groups of comparison: cancer vs. non-cancer, EBV+ vs. EBV- NPC, and metastatic vs. non-metastatic NPC. We constructed a ceRNA network composed of mRNAs, miRNAs, and circRNAs, leveraging co-expression and miRNA target prediction tools. Within the network, we identified the regulatory ceRNAs of CDKN1B, ZNF302, ZNF268, and RPGR. These differentially expressed axis, along with other miRNA-circRNA pairs we identified through our analysis, helps elucidate the genetic and epigenetic changes central to NPC progression, and the differences between EBV+ and EBV- NPC.

scholarly journals Epstein-Barr Virus Mediated Signaling in Nasopharyngeal Carcinoma Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2441 ◽  
Author(s):  
Timmy Richardo ◽  
Pongphol Prattapong ◽  
Chawalit Ngernsombat ◽  
Nurulfitri Wisetyaningsih ◽  
Hisashi Iizasa ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Southeast Asia ◽  
Signaling Pathways ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Non Coding Rnas ◽  
Epstein Barr ◽  
Exact Relationship

Nasopharyngeal carcinoma (NPC) is one of the most common tumors occurring in China and Southeast Asia. Etiology of NPC seems to be complex and involves many determinants, one of which is Epstein-Barr virus (EBV) infection. Although evidence demonstrates that EBV infection plays a key role in NPC carcinogenesis, the exact relationship between EBV and dysregulation of signaling pathways in NPC needs to be clarified. This review focuses on the interplay between EBV and NPC cells and the corresponding signaling pathways, which are modulated by EBV oncoproteins and non-coding RNAs. These altered signaling pathways could be critical for the initiation and progression of NPC.

scholarly journals Epstein-Barr Virus BART Long Non-coding RNAs Function as Epigenetic Modulators in Nasopharyngeal Carcinoma

2019 ◽  
Vol 9 ◽  
Author(s):  
Rob J. A. Verhoeven ◽  
Shuang Tong ◽  
Bobo Wing-Yee Mok ◽  
Jiayan Liu ◽  
Songtao He ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

The effect of lysosomal-associated membrane protein-1-targeting of Epstein–Barr virus nuclear antigen 1 (EBNA1) on immune response and tumor growth in preclinical studies.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 74-74
Author(s):  
Pratima Sinha ◽  
Claire Buchta Rosean ◽  
Teri Heiland
Keyword(s):  
T Cells ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Treatment Strategies ◽  
T Cell Response ◽  
Nuclear Antigen ◽  
Effector Memory ◽  
Combination Strategy ◽  
Barr Virus ◽  
Epstein Barr

74 Background: Epstein-Barr virus (EBV) is an oncogenic γ-herpes virus that infects > 90% of the global population. EBV is the primary cause of infectious mononucleosis and is associated with several epithelial and lymphoid malignancies, including nasopharyngeal carcinoma, gastric carcinoma, non-Hodgkin’s and Hodgkin’s lymphoma. Of these, nasopharyngeal carcinoma is particularly prevalent in East and Southeast Asia and is highly metastatic. Current treatment strategies for nasopharyngeal carcinoma are limited to radiation and chemotherapy, demonstrating a need for new, targeted therapies. Most nasopharyngeal carcinomas express EBNA1, a DNA-binding protein involved in maintenance of the episomal virus genome that is required for EBV latency and associated transformation. Targeting EBNA1 allows for an immunotherapeutic approach, by exploiting the potential of the immune system to recognize tumor cells through their expression of this viral antigen. Methods: We designed a DNA vaccine encoding EBNA1 using the UNITE (UNiversal Intracellular Targeted Expression) platform. The UNITE platform is based in part on lysosomal targeting technology which results in enhanced antigen presentation and a balanced T cell response. Results: We report that the EBNA1-UNITE vaccine induced IFNγ-producing effector memory (EM) CD4+ T and CD8+ T cells with complete rejection of EBNA1-expressing tumors observed in 50% of mice. Mice rejecting tumors were protected from rechallenge with CT26-EBNA1, demonstrating that antigen-specific memory was induced in these animals. Tumor microenvironment (TME) analysis showed vaccine-induced mobilization of effector cells, including tumor infiltration of IL-12-producing type 1 dendritic cells, iNOS-producing M1 macrophages, activated EM CD4+T, and CD8+TNFα+T cells. Furthermore, increased PD-1+CD8+T cells in the TME suggests that a combination strategy with PD-1/PD-L1 blockade may be beneficial in a therapeutic setting. Conclusions: This pre-clinical data suggests that the EBNA1-UNITE vaccine has the potential to be used as an immunotherapeutic agent against EBV-associated cancers.

Studies of Epstein-Barr Virus Antigens Using Immunoperoxidase and Immunofluorescence Techniques

1975 ◽  
Vol 33 ◽  
pp. 342-343
Author(s):  
R. Stephens ◽  
K. Traul ◽  
D. Woolf ◽  
P. Gaudreau
Keyword(s):  
Electron Microscopy ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
If Technique ◽  
Infected Cells ◽  
Virus Antigens ◽  
Epstein Barr ◽  
Virus Capsid Antigen ◽  
Antigen Reactivity

A number of antigens have been found associated with persistent EBV infections of lymphoblastoid cells. Identification and localization of these antigens were principally by immunofluorescence (IF) techniques using sera from patients with nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL), and infectious mononucleosis (IM). Our study was mainly with three of the EBV related antigens, a) virus capsid antigen (VCA), b) membrane antigen (MA), and c) early antigens (EA) using immunoperoxidase (IP) techniques with electron microscopy (EM) to elucidate the sites of reactivity with EBV and EBV infected cells.Prior to labeling with horseradish peroxidase (HRP), sera from NPC, IM, and BL cases were characterized for various reactivities by the indirect IF technique. Modifications of the direct IP procedure described by Shabo and the indirect IP procedure of Leduc were made to enhance penetration of the cells and preservation of antigen reactivity.

scholarly journals Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Amina Gihbid ◽  
Raja Benzeid ◽  
Abdellah Faouzi ◽  
Jalal Nourlil ◽  
Nezha Tawfiq ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Disease Stage ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Pre Treatment ◽  
Moroccan Patients

Abstract Background The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. Methods The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. Results Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. Conclusions The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.

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