鼻咽癌
增强子
小RNA
生物
病毒
爱泼斯坦-巴尔病毒
转录因子
癌症研究
免疫系统
基因
抄写(语言学)
病毒学
免疫学
医学
遗传学
哲学
放射治疗
内科学
语言学
作者
Jie Wang,Junshang Ge,Yian Wang,Fang Xiong,Jiayue Guo,Xianjie Jiang,Lishen Zhang,Xiaolei Deng,Zhaojian Gong,Shanshan Zhang,Qijia Yan,Yi He,Xiayu Li,Lei Shi,Can Guo,Fuyan Wang,Li Zheng,Ming Zhou,Bo Xiang,Yong Li,Wei Xiong
标识
DOI:10.1038/s41467-022-28479-2
摘要
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.
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