IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52201-z.html
   My bibliography  Save this article

USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling

Author

Listed:
  • Mengru Ma

    (Huazhong University of Science and Technology)

  • Lian Yi

    (Huazhong University of Science and Technology)

  • Yifei Pei

    (Huazhong University of Science and Technology)

  • Qimin Zhang

    (University of Electronic Science and Technology of China)

  • Chao Tong

    (Huazhong University of Science and Technology)

  • Manyu Zhao

    (Huazhong University of Science and Technology)

  • Yuanhong Chen

    (Huazhong University of Science and Technology)

  • Jinghan Zhu

    (Huazhong University of Science and Technology)

  • Wanguang Zhang

    (Huazhong University of Science and Technology)

  • Fan Yao

    (Huazhong Agricultural University)

  • Pengyuan Yang

    (Chinese Academy of Sciences)

  • Peijing Zhang

    (University of Electronic Science and Technology of China)

Abstract

Despite recent advances in systemic therapy for hepatocellular carcinoma (HCC), the prognosis of hepatitis B virus (HBV)-induced HCC patients remains poor. By screening a sgRNA library targeting human deubiquitinases, we find that ubiquitin-specific peptidase 26 (USP26) deficiency impairs HBV-positive HCC cell proliferation. Genetically engineered murine models with Usp26 knockout confirm that Usp26 drives HCC tumorigenesis. Mechanistically, we find that the HBV-encoded protein HBx binds to the promoter and induces the production of USP26, which is an X-linked gene exclusively expressed in the testis. HBx consequently promotes the association of USP26 with SIRT1 to synergistically stabilize SIRT1 by deubiquitination, which promotes cell proliferation and impedes cell apoptosis to accelerate HCC tumorigenesis. In patients with HBV-positive HCC, USP26 is robustly induced, and its levels correlate with SIRT1 levels and poor prognosis. Collectively, our study highlights a causative link between HBV infection, deubiquitinase induction and development of HCC, identifying a druggable target, USP26.

Suggested Citation

  • Mengru Ma & Lian Yi & Yifei Pei & Qimin Zhang & Chao Tong & Manyu Zhao & Yuanhong Chen & Jinghan Zhu & Wanguang Zhang & Fan Yao & Pengyuan Yang & Peijing Zhang, 2024. "USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52201-z
    DOI: 10.1038/s41467-024-52201-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52201-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-52201-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Qing Li & Liren Zhang & Wenhua You & Jiali Xu & Jingjing Dai & Dongxu Hua & Ruizhi Zhang & Feifan Yao & Suiqing Zhou & Wei Huang & Yongjiu Dai & Yu Zhang & Tasiken Baheti & Xiaofeng Qian & Liyong Pu &, 2022. "PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Zhen Ning & Xin Guo & Xiaolong Liu & Chang Lu & Aman Wang & Xiaolin Wang & Wen Wang & Huan Chen & Wangshu Qin & Xinyu Liu & Lina Zhou & Chi Ma & Jian Du & Zhikun Lin & Haifeng Luo & Wuxiyar Otkur & Hu, 2022. "USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Pedro A. Pérez-Mancera & Alistair G. Rust & Louise van der Weyden & Glen Kristiansen & Allen Li & Aaron L. Sarver & Kevin A. T. Silverstein & Robert Grützmann & Daniela Aust & Petra Rümmele & Thomas K, 2012. "The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma," Nature, Nature, vol. 486(7402), pages 266-270, June.
    4. Liang Yang & Junfeng Shen & Chunhua Liu & Zhonghua Kuang & Yong Tang & Zhengjiang Qian & Min Guan & Yongfeng Yang & Yang Zhan & Nan Li & Xiang Li, 2023. "Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Ruidong Xue & Qiming Zhang & Qi Cao & Ruirui Kong & Xiao Xiang & Hengkang Liu & Mei Feng & Fangyanni Wang & Jinghui Cheng & Zhao Li & Qimin Zhan & Mi Deng & Jiye Zhu & Zemin Zhang & Ning Zhang, 2022. "Liver tumour immune microenvironment subtypes and neutrophil heterogeneity," Nature, Nature, vol. 612(7938), pages 141-147, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jiaoling Chen & Yaxing Bai & Ke Xue & Zhiguo Li & Zhenlai Zhu & Qingyang Li & Chen Yu & Bing Li & Shengxian Shen & Pei Qiao & Caixia Li & Yixin Luo & Hongjiang Qiao & Erle Dang & Wen Yin & Johann E. G, 2023. "CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Kinzy Tyler G. & Starr Timothy K. & Tseng George C. & Ho Yen-Yi, 2019. "Meta-analytic framework for modeling genetic coexpression dynamics," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 18(1), pages 1-13, February.
    3. Li Yuan & Guo-Dong Jia & Xiao-Fei Lv & Si-Yi Xie & Shan-Shan Guo & Da-Feng Lin & Li-Ting Liu & Dong-Hua Luo & Yi-Fu Li & Shen-Wen Deng & Ling Guo & Mu-Sheng Zeng & Xiu-Yu Cai & Sai-Lan Liu & Xue-Song , 2023. "Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Ying Liao & Yan-Xia Wu & Minzhong Tang & Yi-Wei Chen & Jin-Ru Xie & Yan Du & Tong-Min Wang & Yong-Qiao He & Wen-Qiong Xue & Xiao-Hui Zheng & Qiao-Yun Liu & Mei-Qi Zheng & Yi-Jing Jia & Xia-Ting Tong &, 2024. "Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Christel F. A. Ramirez & Daniel Taranto & Masami Ando-Kuri & Marnix H. P. Groot & Efi Tsouri & Zhijie Huang & Daniel Groot & Roelof J. C. Kluin & Daan J. Kloosterman & Joanne Verheij & Jing Xu & Seren, 2024. "Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    6. Sarah Cappuyns & Gino Philips & Vincent Vandecaveye & Bram Boeckx & Rogier Schepers & Thomas Van Brussel & Ingrid Arijs & Aurelie Mechels & Ayse Bassez & Francesca Lodi & Joris Jaekers & Halit Topal &, 2023. "PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Jiahui Jiang & Yunhe Liu & Jiangjiang Qin & Jianfeng Chen & Jingjing Wu & Melissa P. Pizzi & Rossana Lazcano & Kohei Yamashita & Zhiyuan Xu & Guangsheng Pei & Kyung Serk Cho & Yanshuo Chu & Ansam Sinj, 2024. "METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Xin Yuan & Yanran Ma & Ruitian Gao & Shuya Cui & Yifan Wang & Botao Fa & Shiyang Ma & Ting Wei & Shuangge Ma & Zhangsheng Yu, 2024. "HEARTSVG: a fast and accurate method for identifying spatially variable genes in large-scale spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Yin Li & Manling Jiang & Ling Aye & Li Luo & Yong Zhang & Fengkai Xu & Yongqi Wei & Dan Peng & Xiang He & Jie Gu & Xiaofang Yu & Guoping Li & Di Ge & Chunlai Lu, 2024. "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    10. Yuan Jiang & Yueyuan Zheng & Yuan-Wei Zhang & Shuai Kong & Jinxiu Dong & Fei Wang & Benjamin Ziman & Sigal Gery & Jia-Jie Hao & Dan Zhou & Jianian Zhou & Allen S. Ho & Uttam K. Sinha & Jian Chen & Shu, 2024. "Reciprocal inhibition between TP63 and STAT1 regulates anti-tumor immune response through interferon-γ signaling in squamous cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52201-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.