Establishment and characterization of an Epstein-Barr virus-positive cell line from a non-keratinizing differentiated primary nasopharyngeal carcinoma
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PROVIDER: EGAS00001007172 | EGA |
REPOSITORIES: EGA
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Project description:Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing (WGS) revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing (WGBS) and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively. Drug screening of NPC268 together with six other NPC cell lines using 339 compounds, representing the largest high-throughput drug testing in NPC, revealed biomarkers associated with specific drug classes. NPC268 represents the first and only available EBV-positive non-keratinizing differentiated NPC model, and extensive genomic, methylomic, transcriptomic, and drug response data should facilitate research in EBV and NPC, where current models are limited.
2024-03-13 | GSE233426 | GEO
Project description:MicroRNAs (miRNAs) represent a conserved class of small non-coding RNAs that are found in all higher eukaryotes as well as some DNA viruses. MiRNAs are 20-25 nucleotides (nt) in length and have important regulatory functions in biological processes such as embryonic development, cell differentiation, hormone secretion or metabolism. Furthermore, miRNAs have been implicated in the pathology of various diseases including cancer. MiRNA expression profiles not only classify different types of cancer but also may even help to characterize distinct tumor stages, therefore constituting a valuable tool for prognosis. Here we report the miRNA profile of Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) tissue samples characterized by cloning and sequencing. We find that all EBV miRNAs from the BART region are expressed in NPC tissues whereas ebv-miRNAs from the BHRF1 region are not found. Moreover, we identify two novel EBV miRNA genes originating from the BART region that have not been found in other tissues or cell lines before. We also identify three new human miRNAs, which might be specific for nasopharyngeal tissues. We further show that a number of different cellular miRNAs are upor down-regulated in NPC tissues compared to control tissue including miR-15a and miR-16. We find that the tumor suppressor BRCA-1 is a target of miR-15a as well as miR-16 suggesting a miRNA role in NPC pathogenesis. 2 pairs of NPC and control tissues from 2 patients (4 samples in total) were examined.
2009-02-07 | E-GEOD-14738 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) represent a conserved class of small non-coding RNAs that are found in all higher eukaryotes as well as some DNA viruses. MiRNAs are 20-25 nucleotides (nt) in length and have important regulatory functions in biological processes such as embryonic development, cell differentiation, hormone secretion or metabolism. Furthermore, miRNAs have been implicated in the pathology of various diseases including cancer. MiRNA expression profiles not only classify different types of cancer but also may even help to characterize distinct tumor stages, therefore constituting a valuable tool for prognosis. Here we report the miRNA profile of Epstein-Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) tissue samples characterized by cloning and sequencing. We find that all EBV miRNAs from the BART region are expressed in NPC tissues whereas ebv-miRNAs from the BHRF1 region are not found. Moreover, we identify two novel EBV miRNA genes originating from the BART region that have not been found in other tissues or cell lines before. We also identify three new human miRNAs, which might be specific for nasopharyngeal tissues. We further show that a number of different cellular miRNAs are upor down-regulated in NPC tissues compared to control tissue including miR-15a and miR-16. We find that the tumor suppressor BRCA-1 is a target of miR-15a as well as miR-16 suggesting a miRNA role in NPC pathogenesis.
2009-02-07 | GSE14738 | GEO
Project description:Our appreciation for the extent of Epstein Barr virus (EBV) transcriptome complexity continues to grow through findings of EBV encoded microRNAs, new long non-coding RNAs, and hundreds of new polyadenylated lytic transcripts. Here we report an additional layer to the EBV transcriptome through the identification of a repertoire of latent and lytic viral circRNAs. Utilizing RNase R-sequencing with cell models representing latency types I, II, and III, we identified circRNAs expressed from the latency Cp promoter involving backsplicing from the W1 and W2 exons to the C1 exon, from the EBNA BamHI U exon, and from the latency long-non-coding RPMS1 locus. We also identified circRNAs expressed during reactivation including an exon 8-to-2 backspliced LMP2 transcript and a highly expressed circRNA derived from the BHLF1 gene. Altogether we identified over 30 EBV circRNA candidates and validated and determined the structural features, expression profiles and nuclear-cytoplasmic distributions of several prominent viral circRNAs. Further, we show that two RPMS1 circRNAs are expressed in stomach cancer specimens. This study increases the known EBV latency and lytic transcriptome repertoires to include viral circRNAs and provides an essential foundation for investigations into the functions of this new class of EBV transcripts in EBV biology and disease.
2018-07-12 | GSE116675 | GEO
Project description:Comprehensive Profiling of Epstein-Barr Virus-Encoded miRNAome Associated with Specific Latent Type in Tumor Cells Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expressed different genes associated with three latent types. So far as many as 44 EBV-encoded miRNA species have been found but their comprehensive and comparative profiling is not well documented in three latent infection states linked to various tumor cells. In this study, we utilized the polyA-tailed quantitative real time RT-PCR procedure to measure the relative abundance of viral miRNA species that linked to individual viral genome locations in combination with microarray evaluation in a subset of representative lymphoid and epithelial tumor cells undergoing various types of EBV latent infection. The results showed that miR-BHRF1 family and miR-BART family are expressed differentially in a tissue-dependent and latency-dependent manner. In particular, in NPC tissue and the only EBV consistently harboring cell line C666-1 with latency type II, there were highly abundant miR-BART family but not miR-BHRF1 family members that accounted for more than 10% of the whole known human miRNA library, implicating their important roles in maintaining EBV latent infection and driving NPC tumorigenesis. In addition, EBV miRNAome-based clustering analysis could classify three distinct EBV latency types, meanwhile, for the first time, we found and subsequently evaluated a novel secret latent switch in BL cell line Daudi from type I to III, which was unable to be identified by traditional latent biomarkers. Together, our data provided an in-depth and comparative profiling of EBV miRNA transcriptome in correspondence with three EBV latent infections, suggesting that different viral miRNA species were involved in divergent host cell carcinogenesis. Finally, EBV miRNAome, as a cluster of novel latency biomarkers expressed variedly in tumor cells, greatly complements and improves the classical typing criteria in conjunction with other latently expressed marker genes. 2 NPC tissue samples and 2 NPC cell lines and 5 lymphocytic cell lines
2012-07-06 | E-GEOD-33225 | biostudies-arrayexpress
Project description:Whether the human tumor virus, Epstein-Barr virus (EBV) promotes breast cancers remains controversial and a potential mechanism has remained elusive. Here we show EBV can infect primary mammary epithelial cells (MECs) that express the attachment receptor, CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, including expression of latent membrane proteins 1 (LMP1) and 2 (LMP2), similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for EBVness was generated based on the RNA expression profile of the EBV infected primary mammary epithelial cells, tumors. This was signature associated with high grade (40 vs 13.5%) estrogen-receptor-negative status (31.8 vs. 10.5%, p53 mutation (37.5 vs 14.5%) and poor survival. In 11/33 (33%) of tumors positive for EBVness EBV-DNA was found in tumor cells by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes, while only 4/36 (11%) of EBVness-negative tumors tested positive for EBV DNA. An analysis of the TCGA breast cancer data revealed a correlation of EBVness with presence of the APOBEC mutational signatures consistent with past viral infection. We conclude that a contribution of EBV to breast cancer etiology via a ‘hit-and-run’ mechanism is plausible, in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is not required for the maintenance of the malignant phenotype.
2016-05-04 | GSE81068 | GEO
Project description:Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). Phorbol esters, butyrates and N-nitroso compounds are known chemical carcinogens in foodstuffs and cigarettes that have been implicated as risk factors contributing to the development of NPC. We have demonstrated previously that low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.1 microg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate (SB) in enhancing EBV reactivation (Chem Biol Interact 188: 623-634). Since residents of areas with a high risk of NPC are reported to contact with these carcinogens (TPA, SB or nitrosamines) frequently, we sought to determine the consequence of repeated exposure of EBV-harboring nasopharyngeal cells to these carcinogens in a long-term, low dose, repeated manner. An NPC cell line latently infected with EBV, NA, was periodically treated with TPA/SB combined with MNNG for recurrent EBV reactivation. After 10 times of chemically-induced recurrent reactivation of EBV, the expression profile analysis indicates that many carcinogenesis-related genes were altered in recurrent reactivated NA cells when compared to the parental NA cells. The expression profile was analyzed in the recurrent EBV reactivated NA cells and the parental NA cells.
2012-08-15 | GSE38453 | GEO
Project description:<p>Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression, and rational therapy design. Here, we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-kB pathway in a total of 41% of cases including CYLD, TRAF3, NFKBIA and NLRC5. Functional analysis confirmed novel inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent member protein 1 (LMP1) functions to constitutively activate NF-kB signaling, and we observed mutual exclusivity among somatic NF-kB pathway aberrations and LMP1-overexpression, suggesting that NF-kB activation is selected for by both somatic and viral events during NPC pathogenesis.</p>
| phs001244 | dbGaP
Project description:Expression of mRNAs in EBV-positive B-cell strains in the presence or absence of EBNA1 or a mutant of EBNA1 (ΔUR1-EBNA) that is unable to activate transcription.
2021-11-12 | GSE75198 | GEO
Project description:Epstein Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B-cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain novel insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B-cell proteome and EBV virome. Our approach revealed EBV-induced remodelling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B-cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi sarcoma associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication.
2017-05-19 | PXD006317 | Pride