The novel functional effects of exogenous EBV-miR-BARTs on NPC progression
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA184667PRJNA184666PRJNA184665
ORGANISM(S): Macacine gammaherpesvirus 4 Mus musculus Human gammaherpesvirus 8 Rattus norvegicus Betapolyomavirus macacae Homo sapiens
PROVIDER: GSE42945 | GEO | 2015/06/30
SECONDARY ACCESSION(S): PRJNA184665
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-01-04 | GSE200794 | GEO
Project description:Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV- positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-03-01 | E-GEOD-26212 | biostudies-arrayexpress
Project description:Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and southern China. The primary treatment for NPC is radiotherapy. Despite of the encouraging results of radiotherapy, local recurrence or distant metastases of NPC after the initial therapy is frequently found due to radioresistance. Therefore, there is an urgent need to identify genes that control radiosensitivty, aiming to reduce disease recurrence. Epstein-Barr virus (EBV) infection was closely associated with undifferentiated NPC. EBV-encoded microRNAs (miRNAs) played crucial roles in the pathogenesis of NPC. Ebv-miR-BART7 belongs to the 44 EBV BART miRNAs and was found to be up-regulated in NPC tissues and plasma. Forced expression of ebv-miR-BART7 enhanced the radiosensitivity of NPC cells. However, the mechanisms underlying the sensitizing effect of ebv-miR-BART7 on radiation remain largely unknown. Given that miRNA exerts biological functions by regulating its targets, we used microarray to identify the targets of ebv-miR-BART7 that regulate radiosensitivity of NPC cells.
2017-03-31 | GSE79571 | GEO
Project description:PURPOSE:Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. EXPERIMENTAL DESIGN:We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated. RESULTS:A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. CONCLUSIONS:Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.
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Project description:Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC.
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Project description:Nasopharyngeal carcinoma (NPC) is an invasive head-and-neck tumor with Epstein-Barr virus (EBV) as an important etiological cause. The EBV oncoprotein Latent membrane protein 1 (LMP1) can be trafficked into exosomes with unclear roles, and this trafficking is a potential problem in NPC control. MicroRNA-203 (miR-203) was found by us to be downregulated by LMP1, and it functions as a tumor suppressor in NPC. In this study, aspirin reversed the epithelial-mesenchymal transition (EMT) by promoting miR-203 expression in cells, and, remarkably, it repressed exosomal LMP1 (exo-LMP1) secretion from EBV-positive cells. Nuclear factor κB (NF-κB) activation was required for the exo-LMP1 production. The exo-LMP1 uptake influenced the EMT potential of EBV-negative recipient NPC cells. The exo-LMP1 level was upregulated in clinical NPC plasma samples. Aspirin treatment observably inhibited NPC lung metastasis in nude mice. The study revealed that aspirin is a promising drug for NPC therapy via its targeting of exo-LMP1 transfer and the regulatory effect of LMP1 on miR-203 expression. EBV can regulate its own tumorigenesis via the LMP1/NF-κB/exo-LMP1 axis, opening a new avenue for understanding the pathogenesis of this tumor virus. Our study also provides a rationale for the use of exo-LMP1 or exosomal miR-203 (exo-miR203) in EBV-targeted therapy by aspirin in invasive NPC.
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Project description:Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-08-03 | GSE166750 | GEO
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2011-03-01 | GSE26212 | GEO