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Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE225251 | GEO | 2024/03/27

REPOSITORIES: GEO

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Enhancer infestation drives tumorigenic activation of inactive B compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma.

Project description:BackgroundNasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignant epithelial tumor endemic to Southern China and Southeast Asia. While previous studies have revealed a low frequency of gene mutations in NPC, its epigenomic aberrations are not fully elucidated apart from DNA hypermethylation. Epigenomic rewiring and enhancer dysregulation, such as enhancer hijacking due to genomic structural changes or extrachromosomal DNA, drive cancer progression.MethodsWe conducted Hi-C, 4C-seq, ChIP-seq, and RNA-seq analyses to comprehensively elucidate the epigenome and interactome of NPC using C666-1 EBV(+)-NPC cell lines, NP69T immortalized nasopharyngeal epithelial cells, clinical NPC biopsy samples, and in vitro EBV infection in HK1 and NPC-TW01 EBV(-) cell lines.FindingsIn C666-1, the EBV genome significantly interacted with inactive B compartments of host cells; the significant association of EBV-interacting regions (EBVIRs) with B compartment was confirmed using clinical NPC and in vitro EBV infection model. EBVIRs in C666-1 showed significantly higher levels of active histone modifications compared with NP69T. Aberrant activation of EBVIRs after EBV infection was validated using in vitro EBV infection models. Within the EBVIR-overlapping topologically associating domains, 14 H3K4me3(+) genes were significantly upregulated in C666-1. Target genes of EBVIRs including PLA2G4A, PTGS2 and CITED2, interacted with the enhancers activated in EBVIRs and were highly expressed in NPC, and their knockdown significantly reduced cell proliferation.InterpretationThe EBV genome contributes to NPC tumorigenesis through "enhancer infestation" by interacting with the inactive B compartments of the host genome and aberrantly activating enhancers.FundingThe funds are listed in the Acknowledgements section.

| S-EPMC10951899 | biostudies-literature

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [RNA-Seq]

Project description:We analyzed the gene expressions around the host genomic regions where EBV and host genomic interactions were obsearved in nasopharyngeal carcinoma cell lines.

2024-03-27 | GSE225250 | GEO

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [Hi-C]

Project description:We analyzed the compartment status and chromatin interactions in nasopharyngeal epithelial cell lines and nasopharyngeal carcinoma cell lines by performing Hi-C.

2024-03-27 | GSE225249 | GEO

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [ChIP-Seq]

Project description:We analyzed active enhancers of nasopharyngeal epithelial cell lines and nasopharyngeal carcinoma cell lines by performing ChIP-seq on H3K4me1, H3K4me3, and H3K27ac.

2024-03-27 | GSE225248 | GEO

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [4C-Seq]

Project description:We detected the EBV interaction regions and the genomic loops from TSS of PLA2G4A in nasopharyngeal carcinoma cell lines by 4C-seq analysis.

2024-03-27 | GSE225247 | GEO

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma

Project description:Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma

| PRJNA934673 | ENA

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [ChIP-Seq]

Project description:Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [ChIP-Seq]

| PRJNA934676 | ENA

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [4C-Seq]

Project description:Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [4C-Seq]

| PRJNA934680 | ENA

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [Hi-C]

Project description:Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [Hi-C]

| PRJNA934678 | ENA

Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [RNA-Seq]

Project description:Enhancer infestation drives tumorigenic activation of inactive compartment in Epstein-Barr virus-positive nasopharyngeal carcinoma [RNA-Seq]

| PRJNA934679 | ENA

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