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EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1

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  • Jie Wang

    (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
    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)

  • Junshang Ge

    (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)

  • Yian Wang

    (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)

  • Fang Xiong

    (Xiangya Hospital, Central South University)

  • Jiayue Guo

    (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)

  • Xianjie Jiang

    (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)

  • Lishen Zhang

    (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)

  • Xiangying Deng

    (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)

  • Zhaojian Gong

    (The Second Xiangya Hospital, Central South University)

  • Shanshan Zhang

    (Xiangya Hospital, Central South University)

  • Qijia Yan

    (Xiangya Hospital, Central South University)

  • Yi He

    (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)

  • Xiayu Li

    (Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University)

  • Lei Shi

    (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
    The Second Xiangya Hospital, Central South University)

  • Can Guo

    (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)

  • Fuyan Wang

    (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)

  • Zheng Li

    (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)

  • Ming Zhou

    (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)

  • Bo Xiang

    (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)

  • Yong Li

    (Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine)

  • Wei Xiong

    (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
    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)

  • Zhaoyang Zeng

    (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
    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)

Abstract

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.

Suggested Citation

  • Jie Wang & Junshang Ge & Yian Wang & Fang Xiong & Jiayue Guo & Xianjie Jiang & Lishen Zhang & Xiangying Deng & Zhaojian Gong & Shanshan Zhang & Qijia Yan & Yi He & Xiayu Li & Lei Shi & Can Guo & Fuyan, 2022. "EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28479-2
    DOI: 10.1038/s41467-022-28479-2
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    Cited by:

    1. Junshang Ge & Yi Meng & Jiayue Guo & Pan Chen & Jie Wang & Lei Shi & Dan Wang & Hongke Qu & Pan Wu & Chunmei Fan & Shanshan Zhang & Qianjin Liao & Ming Zhou & Bo Xiang & Fuyan Wang & Ming Tan & Zhaoji, 2024. "Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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