Dataset Information

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.

ABSTRACT:

Background

Epstein-Barr virus (EBV) is the first discovered human tumor virus that is associated with a variety of malignancies of both lymphoid and epithelial origin including nasopharyngeal carcinoma (NPC). The EBV-encoded latent membrane protein 1 (LMP1) has been well-defined as a potent oncogenic protein, which is intimately correlated with NPC pathogenesis. Anoikis is considered to be a physiological barrier to metastasis, and avoiding anoikis is a major hallmark of metastasis. However, the role of LMP1 in anoikis-resistance and metastasis of NPC has not been fully identified.

Methods

Trypan blue staining, colony formation assay, flow cytometry, and TUNEL staining, as well as the detection of apoptosis and anoikis resistance-related markers was applied to evaluate the anoikis-resistant capability of NPC cells cultured in ultra-low adhesion condition. Co-immunoprecipitation (Co-IP) experiment was performed to determine the interaction among LMP1, PRMT1 and PGC-1α. Ex vivo ubiquitination assay was used to detect the ubiquitination level of PGC-1α. Anoikis- resistant LMP1-positive NPC cell lines were established and applied for the xenograft and metastatic animal experiments.

Results

Our current findings reveal the role of LMP1-stabilized peroxisome proliferator activated receptor coactivator-1a (PGC-1α) in anoikis resistance and immune escape to support the invasion and metastasis of NPC. Mechanistically, LMP1 enhances PGC-1α protein stability by promoting the interaction between arginine methyltransferase 1 (PRMT1) and PGC-1α to elevate the methylation modification of PGC-1α, thus endowing NPC cells with anoikis-resistance. Meanwhile, PGC-1α mediates the immune escape induced by LMP1 by coactivating with STAT3 to transcriptionally up-regulate PD-L1 expression.

Conclusion

Our work provides insights into how virus-encoded proteins recruit and interact with host regulatory elements to facilitate the malignant progression of NPC. Therefore, targeting PGC-1α or PRMT1-PGC-1α interaction might be exploited for therapeutic gain for EBV-associated malignancies.

SUBMITTER: Liao C

PROVIDER: S-EPMC10559433 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.

Liao Chaoliang C Li Min M Chen Xue X Tang Chenpeng C Quan Jing J Bode Ann M AM Cao Ya Y Luo Xiangjian X

Journal of experimental & clinical cancer research : CR 20231007 1

<h4>Background</h4>Epstein-Barr virus (EBV) is the first discovered human tumor virus that is associated with a variety of malignancies of both lymphoid and epithelial origin including nasopharyngeal carcinoma (NPC). The EBV-encoded latent membrane protein 1 (LMP1) has been well-defined as a potent oncogenic protein, which is intimately correlated with NPC pathogenesis. Anoikis is considered to be a physiological barrier to metastasis, and avoiding anoikis is a major hallmark of metastasis. Howe ...[more]

PMID: 37803433

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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

Dataset Information

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.

Background

Methods

Results

Conclusion

Publications

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.

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