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Human papillomavirus-encoded circular RNA circE7 promotes immune evasion in head and neck squamous cell carcinoma

Author

Listed:
  • Junshang Ge

    (Central South University
    Central South University
    Central South University)

  • Yi Meng

    (Central South University
    Central South University
    Central South University)

  • Jiayue Guo

    (Central South University
    Central South University
    Central South University)

  • Pan Chen

    (Central South University)

  • Jie Wang

    (Central South University)

  • Lei Shi

    (Central South University)

  • Dan Wang

    (Central South University)

  • Hongke Qu

    (Central South University)

  • Pan Wu

    (Central South University)

  • Chunmei Fan

    (Central South University)

  • Shanshan Zhang

    (Central South University)

  • Qianjin Liao

    (Central South University)

  • Ming Zhou

    (Central South University)

  • Bo Xiang

    (Central South University)

  • Fuyan Wang

    (Central South University)

  • Ming Tan

    (China Medical University)

  • Zhaojian Gong

    (Central South University
    Central South University)

  • Wei Xiong

    (Central South University
    Central South University
    Furong Laboratory)

  • Zhaoyang Zeng

    (Central South University
    Central South University
    Central South University
    Furong Laboratory)

Abstract

Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52981-4
    DOI: 10.1038/s41467-024-52981-4
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    References listed on IDEAS

    as
    1. 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.
    2. Jiawei Zhao & Eunice E. Lee & Jiwoong Kim & Rong Yang & Bahir Chamseddin & Chunyang Ni & Elona Gusho & Yang Xie & Cheng-Ming Chiang & Michael Buszczak & Xiaowei Zhan & Laimonis Laimins & Richard C. Wa, 2019. "Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Moritz Hunkeler & Anna Hagmann & Edward Stuttfeld & Mohamed Chami & Yakir Guri & Henning Stahlberg & Timm Maier, 2018. "Structural basis for regulation of human acetyl-CoA carboxylase," Nature, Nature, vol. 558(7710), pages 470-474, June.
    4. Riyao Yang & Linlin Sun & Ching-Fei Li & Yu-Han Wang & Jun Yao & Hui Li & Meisi Yan & Wei-Chao Chang & Jung-Mao Hsu & Jong-Ho Cha & Jennifer L. Hsu & Cheng-Wei Chou & Xian Sun & Yalan Deng & Chao-Kai , 2021. "Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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