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EBV 编码的 EBER1 和 LMP2A 对 YAP1 的调控机制及 YAP1 对 EBV 相关胃癌中 EBV 感染状态的影响。

Regulation mechanism of EBV-encoded EBER1 and LMP2A on YAP1 and the impact of YAP1 on the EBV infection status in EBV-associated gastric carcinoma.

机构信息

Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China.

Department of Pathogenic Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China; Department of Clinical Laboratory, Zibo Central Hospital, ZiBo 255036, China.

出版信息

Virus Res. 2024 May;343:199352. doi: 10.1016/j.virusres.2024.199352. Epub 2024 Mar 11.

DOI:10.1016/j.virusres.2024.199352
PMID:38462175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10982081/
Abstract

This study aims to explore the role and regulatory mechanism of Yes-associated protein 1 (YAP1) in the development of Epstein-Barr virus-associated gastric cancer (EBVaGC). Here we showed that EBV can upregulate the expression and activity of YAP1 protein through its encoded latent products EBV-encoded small RNA 1 (EBER1) and latent membrane protein 2A (LMP2A), enhancing the malignant characteristics of EBVaGC cells. In addition, we also showed that overexpression of YAP1 induced the expression of EBV encoding latent and lytic phase genes and proteins in the epithelial cell line AGS-EBV infected with EBV, and increased the copy number of the EBV genome, while loss of YAP1 expression reduced the aforementioned indicators. Moreover, we found that YAP1 enhanced EBV lytic reactivation induced by two known activators, 12-O-tetradecanoylhorbol-13-acetate (TPA) and sodium butyrate (NaB). These results indicated a bidirectional regulatory mechanism between EBV and YAP1 proteins, providing new experimental evidence for further understanding the regulation of EBV infection patterns and carcinogenic mechanisms in gastric cancer.

摘要

本研究旨在探讨 Yes 相关蛋白 1（YAP1）在 Epstein-Barr 病毒相关胃癌（EBVaGC）发生发展中的作用及其调控机制。我们发现 EBV 可通过其编码的潜伏产物 EBV 编码的小 RNA1（EBER1）和潜伏膜蛋白 2A（LMP2A）上调 YAP1 蛋白的表达和活性，增强 EBVaGC 细胞的恶性特征。此外，我们还发现，在 EBV 感染的上皮细胞系 AGS-EBV 中，过表达 YAP1 诱导 EBV 编码潜伏和裂解期基因和蛋白的表达，并增加 EBV 基因组的拷贝数，而 YAP1 表达的缺失则降低了上述指标。此外，我们发现 YAP1 增强了两种已知激活剂 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）和丁酸钠（NaB）诱导的 EBV 裂解再激活。这些结果表明 EBV 和 YAP1 蛋白之间存在双向调控机制，为进一步了解 EBV 感染模式和胃癌致癌机制的调控提供了新的实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/fa8c9c638acf/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/a45232038116/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/a96c0cae3701/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/948c0af41c4b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/428ae5140812/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/5d30cc71daf5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/fa8c9c638acf/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/a45232038116/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/a96c0cae3701/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/948c0af41c4b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/428ae5140812/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/5d30cc71daf5/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcd/10982081/fa8c9c638acf/gr6.jpg

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本文引用的文献

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Establishment of Epstein-Barr Virus (EBV) Latent Gene-Expressing T-Cell Lines with an Expression Vector Harboring EBV Nuclear Antigen 1.利用携带EB病毒核抗原1的表达载体建立表达EB病毒潜伏基因的T细胞系。
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