EBV 微小 RNA BART11 和 BART17-3p 通过增强子介导的 PD-L1 转录促进免疫逃逸。
EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1.
机构信息
NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China.
出版信息
Nat Commun. 2022 Feb 14;13(1):866. doi: 10.1038/s41467-022-28479-2.
Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the specific mechanisms underlying the EBV-dependent promotion of PD-L1 expression to induce immune escape warrant clarification. EBV encodes 44 mature miRNAs. In this study, we find that EBV-miR-BART11 and EBV-miR-BART17-3p upregulate the expression of PD-L1 in EBV-associated NPC and GC. Furthermore, EBV-miR-BART11 targets FOXP1, EBV-miR-BART17-3p targets PBRM1, and FOXP1 and PBRM1 bind to the enhancer region of PD-L1 to inhibit its expression. Therefore, EBV-miR-BART11 and EBV-miR-BART17-3p inhibit FOXP1 and PBRM1, respectively, and enhance the transcription of PD-L1 (CD274, http://www.ncbi.nlm.nih.gov/gene/29126 ), resulting in the promotion of tumor immune escape, which provides insights into potential targets for EBV-related tumor immunotherapy.
EB 病毒（EBV）据报道是第一个被发现的人类肿瘤病毒，与鼻咽癌（NPC）、胃癌（GC）和几种淋巴瘤的发生和发展密切相关。PD-L1 在 EBV 阳性 NPC 和 GC 组织中表达上调；然而，需要阐明 EBV 依赖性促进 PD-L1 表达以诱导免疫逃逸的具体机制。EBV 编码 44 个成熟的 miRNA。在本研究中，我们发现 EBV-miR-BART11 和 EBV-miR-BART17-3p 上调 EBV 相关 NPC 和 GC 中 PD-L1 的表达。此外，EBV-miR-BART11 靶向 FOXP1，EBV-miR-BART17-3p 靶向 PBRM1，FOXP1 和 PBRM1 结合到 PD-L1 的增强子区域抑制其表达。因此，EBV-miR-BART11 和 EBV-miR-BART17-3p 分别抑制 FOXP1 和 PBRM1，并增强 PD-L1（CD274，http://www.ncbi.nlm.nih.gov/gene/29126）的转录，从而促进肿瘤免疫逃逸，为 EBV 相关肿瘤免疫治疗提供了潜在靶点。
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