Epstein–Barr virus-encoded microRNA BART22 serves as novel biomarkers and drives malignant transformation of nasopharyngeal carcinoma

Zhang, Ting; Chen, Zui; Deng, Jing; Xu, Kaixiong; Che, Di; Lin, Jheng-Hua; Jiang, Ping; Gu, Xiaoqiong; Xu, Banglao

doi:10.1038/s41419-022-05107-x

Cited by 12 publications

(12 citation statements)

References 63 publications

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“…Regulates TGF-β1/ ZEB / miR-200 feedback loop (Li et al, 2014b) LMP1 Regulates Snail and Twist (Horikawa et al, 2007(Horikawa et al, , 2011; Enhances calreticulin expression (Ye et al, 2020); Induces hypermethylation of CDH1 (Tsai et al, 2002(Tsai et al, , 2006; Enhances the expression and activity of MMP9 (Takeshita et al, 1999) LMP2A Mediates MTA1 (Lin et al, 2014); Regulates the integrin β4 (ITGβ4) subunit (Zhou et al, 2014;Liang et al, 2017); Enhances the expression of MMP9 (Lan et al, 2012) miR-BART7-3p Targets PTEN (Cai et al, 2015) miR-BART8-3p Targets RNF38 (Lin et al, 2018a) miR-BART9 Targets E-cadherin (Hsu et al, 2014) miR-BART10-3p Targets BTRC (Yan et al, 2015) miR-BART13-3p Targets ABI2 (Huang et al, 2020) miR-BART22 Targets MOSPD2 (Zhang et al, 2022) Metabolic reprogramming LMP1 Enhances GLUT1 transcription (Zhang et al, 2017); Induces FGFR1 expression and activation (Lo et al, 2015); Modulates c-Myc and HK2 (Xiao et al, 2014); Represses HoxC8 (Jiang et al, 2015) LMP2A Downregulates adipose triglyceride lipase (Zheng et al, 2020) miR-BART1-5p Activates the AMPK/mTOR/HIF1 pathway (Wang et al, 2018) 10.3389/fmicb.2023.1116143…”

Section: Ebna1mentioning

confidence: 99%

“…By mediating the TGF-β1/ zinc finger E-box binding homeobox (ZEB)/ miR-200 feedback loop, EBNA1 induces EMT in NPC ( Li et al, 2014b ). EBV-miR- BART7-3p , BART8-3p , BART10-3p , BART13-3p , and BART22 induce the EMT process by targeting PTEN , RNF38 , BTRC , ABI2 and MOSPD2 genes, respectively, in NPC cells ( Cai et al, 2015 ; Yan et al, 2015 ; Lin et al, 2018a ; Huang et al, 2020 ; Zhang et al, 2022 ).…”

Section: The Pathogenic Role Of Ebv In Npcmentioning

confidence: 99%

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The role of Epstein–Barr virus in nasopharyngeal carcinoma

Siak

Leong³

et al. 2023

Front. Microbiol.

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Nasopharyngeal carcinoma (NPC) is a metastasis-prone malignancy closely associated with the Epstein–Barr virus (EBV). Despite ubiquitous infection of EBV worldwide, NPC incidences displayed predominance in certain ethnic groups and endemic regions. The majority of NPC patients are diagnosed with advanced-stage disease, as a result of anatomical isolation and non-specific clinical manifestation. Over the decades, researchers have gained insights into the molecular mechanisms underlying NPC pathogenesis as a result of the interplay of EBV infection with several environmental and genetic factors. EBV-associated biomarkers were also used for mass population screening for the early detection of NPC. EBV and its encoded products also serve as potential targets for the development of therapeutic strategies and tumour-specific drug delivery. This review will discuss the pathogenic role of EBV in NPC and efforts in exploiting the potential of EBV-associated molecules as biomarkers and therapeutic targets. The current knowledge on the role of EBV and its associated products in NPC tumorigenesis, development and progression will offer a new outlook and potential intervention strategy against this EBV-associated malignancy.

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Section: Ebna1mentioning

confidence: 99%

Section: The Pathogenic Role Of Ebv In Npcmentioning

confidence: 99%

The role of Epstein–Barr virus in nasopharyngeal carcinoma

Siak

Leong³

et al. 2023

Front. Microbiol.

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“…EBNA1 is only one of the numerous non-polyadenylated RNAs found in certain EBV malignant growth cells, which incorporate EBER1 and EBER2. In latent infected epithelial cells, the EBERs self-replicate and bind to the ribosomal protein L22 to deliver ribonucleoprotein particles [ 76 , 77 ]. The complex then connects to the PKR, hindering apoptosis by FAS.…”

Section: Latent Gene Products Of Ebvmentioning

confidence: 99%

“…EBV is also present in a subset of gastric adenocarcinomas and other carcinomas of the salivary glands. As a result, EBV epithelial infection can cause malignant transformation, requiring specific preventive and therapeutic treatments [ 74 , 76 ].…”

Section: Primary Gene Product (Genetic Variability)mentioning

confidence: 99%

Updates on Epstein–Barr Virus (EBV)-Associated Nasopharyngeal Carcinoma: Emphasis on the Latent Gene Products of EBV

et al. 2022

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Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for such changes are unclear. Even though the Epstein–Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to the aberrant establishment of viral latency in these tumors. The early and late phases of NPC patients’ survival rates vary significantly. The presence of EBV in all tumor cells presents prospects for the development of innovative therapeutic and diagnostic techniques, despite the fact that the virus’s exact involvement in the carcinogenic process is presently not very well known. EBV research continues to shed light on the carcinogenic process, which is important for a more comprehensive knowledge of tumor etiology and the development of targeted cancer therapeutics. In order to screen for NPC, EBV-related biomarkers have been widely used in a few high-incidence locations because of their close associations with the risks of NPC. The current review highlights the scientific importance of EBV and its possible association with NPC.

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“…Epstein-Barr virus (EBV) is one of the most common causative agents, and it can be detected in all types of NPC [ 7 ]. Radiotherapy is the primary treatment choice for NPC treatment due to the radiosensitive characteristic of NPC tumor [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a risk prediction model for overall survival in patients with nasopharyngeal carcinoma: a prospective cohort study in China

Miao

Lei

et al. 2022

Cancer Cell Int

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Objective Nasopharyngeal carcinoma (NPC) is prevailing in Southern China, characterized by distinct geographical distribution. Aimed to predict the overall survival (OS) of patients with nasopharyngeal carcinoma, this study developed and validated nomograms considering demographic variables, hematological biomarkers, and oncogenic pathogens in China. Methods The clinicopathological and follow-up data of the nasopharyngeal carcinoma patients obtained from a prospective longitudinal cohort study in the Chongqing University Cancer Hospital between Jan 1, 2017 and Dec 31, 2019 ($$\mathrm{n}=1635$$ n = 1635 ). Cox regression model was used to tested the significance of all available variables as prognostic factors of OS. And independent prognostic factors were identified based on multivariable analysis to model nomogram. Concordance index (C-index), area under the receiver operating characteristic (AUC), calibration curve, and decision curve analysis (DCA) were measured to assess the model performance of nomogram. Results Data was randomly divided into a training cohort (1227 observers, about 70% of data) and a validation group (408 observers, about 30% of data). At multivariable analysis, the following were independent predictors of OS in NPC patients and entered into the nomogram: age (hazard ratio [HR]: 1.03), stage (stage IV vs. stage I–II, HR: 4.54), radiotherapy (Yes vs. No, HR: 0.43), EBV ($$\ge 1000$$ ≥ 1000 vs.$$<1000$$ < 1000 , HR: 1.92), LAR ($$>6.15$$ > 6.15 vs.$$\le 6.15$$ ≤ 6.15 , HR: 2.05), NLR ($$>4.84$$ > 4.84 vs. $$\le 4.84$$ ≤ 4.84 HR: 1.54), and PLR ($$>206.33$$ > 206.33 vs.$$\le 206.33$$ ≤ 206.33 , HR: 1.79). The C-indexes for training cohort at 1-, 3- and 5-year were 0.73, 0.83, 0.80, respectively, in the validation cohort, the C-indexes were 0.74 (95% CI 0.63–0.86), 0.80 (95% CI 0.73–0.87), and 0.77 (95% CI 0.67–0.86), respectively. The calibration curve demonstrated that favorable agreement between the predictions of the nomograms and the actual observations in the training and validation cohorts. In addition, the decision curve analysis proved that the nomogram model had the highest overall net benefit. Conclusion A new prognostic model to predict OS of patients with NPC was developed. This can offer clinicians treatment making and patient counseling. Furthermore, the nomogram was deployed into a website server for use.

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Epstein–Barr virus-encoded microRNA BART22 serves as novel biomarkers and drives malignant transformation of nasopharyngeal carcinoma

Cited by 12 publications

References 63 publications

The role of Epstein–Barr virus in nasopharyngeal carcinoma

The role of Epstein–Barr virus in nasopharyngeal carcinoma

Updates on Epstein–Barr Virus (EBV)-Associated Nasopharyngeal Carcinoma: Emphasis on the Latent Gene Products of EBV

Development and validation of a risk prediction model for overall survival in patients with nasopharyngeal carcinoma: a prospective cohort study in China

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