IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44576-2.html
   My bibliography  Save this article

Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma

Author

Listed:
  • Weiwei Dai

    (Fudan University
    Fudan University)

  • Ruotong Tian

    (Fudan University)

  • Liubing Yu

    (Fudan University
    Fudan University)

  • Shasha Bian

    (Fudan University
    Fudan University)

  • Yuling Chen

    (Fudan University)

  • Bowen Yin

    (Fudan University
    Fudan University)

  • Yuxuan Luan

    (Fudan University
    Fudan University)

  • Siqi Chen

    (Fudan University
    Fudan University)

  • Zhuoyang Fan

    (Fudan University
    Fudan University)

  • Rucheng Yan

    (Fudan University)

  • Xin Pan

    (Fudan University
    National Center of Biomedical Analysis)

  • Yingyong Hou

    (Fudan University)

  • Rong Li

    (Naval Medical University)

  • Juxiang Chen

    (Naval Medical University)

  • Minfeng Shu

    (Fudan University
    Fudan University)

Abstract

Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.

Suggested Citation

  • Weiwei Dai & Ruotong Tian & Liubing Yu & Shasha Bian & Yuling Chen & Bowen Yin & Yuxuan Luan & Siqi Chen & Zhuoyang Fan & Rucheng Yan & Xin Pan & Yingyong Hou & Rong Li & Juxiang Chen & Minfeng Shu, 2024. "Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44576-2
    DOI: 10.1038/s41467-023-44576-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44576-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44576-2?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. Silvia Guglietta & Andrea Chiavelli & Elena Zagato & Carsten Krieg & Sara Gandini & Paola Simona Ravenda & Barbara Bazolli & Bao Lu & Giuseppe Penna & Maria Rescigno, 2016. "Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    2. Nian Liu & Qing Dai & Guanqun Zheng & Chuan He & Marc Parisien & Tao Pan, 2015. "N6-methyladenosine-dependent RNA structural switches regulate RNA–protein interactions," Nature, Nature, vol. 518(7540), pages 560-564, February.
    3. Linbin Yang & Qiang Liu & Xiaoqian Zhang & Xinwei Liu & Boxuan Zhou & Jianing Chen & Di Huang & Jiaqian Li & Heliang Li & Fei Chen & Jiang Liu & Yue Xing & Xueman Chen & Shicheng Su & Erwei Song, 2020. "DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25," Nature, Nature, vol. 583(7814), pages 133-138, July.
    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. Zhiyuan Zheng & Ya-nan Li & Shanfen Jia & Mengting Zhu & Lijuan Cao & Min Tao & Jingting Jiang & Shenghua Zhan & Yongjing Chen & Ping-Jin Gao & Weiguo Hu & Ying Wang & Changshun Shao & Yufang Shi, 2021. "Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Ainara González-Iglesias & Aida Arcas & Ana Domingo-Muelas & Estefania Mancini & Joan Galcerán & Juan Valcárcel & Isabel Fariñas & M. Angela Nieto, 2024. "Intron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Junho Lee & Donggu Lee & Sean Lawler & Yangjin Kim, 2021. "Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model," PLOS Computational Biology, Public Library of Science, vol. 17(2), pages 1-29, February.
    4. Xiang Xia & Zizhen Zhang & Chunchao Zhu & Bo Ni & Shuchang Wang & Shuofei Yang & Fengrong Yu & Enhao Zhao & Qing Li & Gang Zhao, 2022. "Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Lixia Chen & Peiling Dai & Lei Liu & Yujia Chen & Yanxia Lu & Lin Zheng & Haowei Wang & Qinzi Yuan & Xuenong Li, 2024. "The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Raymond K. H. Yip & Joel S. Rimes & Bianca D. Capaldo & François Vaillant & Kellie A. Mouchemore & Bhupinder Pal & Yunshun Chen & Elliot Surgenor & Andrew J. Murphy & Robin L. Anderson & Gordon K. Smy, 2021. "Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    7. Weili Wang & Huizhen Zheng & Jun Jiang & Zhi Li & Dongpeng Jiang & Xiangru Shi & Hui Wang & Jie Jiang & Qianqian Xie & Meng Gao & Jianhong Chu & Xiaoming Cai & Tian Xia & Ruibin Li, 2022. "Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Jasmin Bartl & Marco Zanini & Flavia Bernardi & Antoine Forget & Lena Blümel & Julie Talbot & Daniel Picard & Nan Qin & Gabriele Cancila & Qingsong Gao & Soumav Nath & Idriss Mahoungou Koumba & Mariet, 2022. "The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Xiaochuan Liu & Hao Chen & Zekun Li & Xiaoxiao Yang & Wen Jin & Yuting Wang & Jian Zheng & Long Li & Chenghao Xuan & Jiapei Yuan & Yang Yang, 2024. "InPACT: a computational method for accurate characterization of intronic polyadenylation from RNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. Guanqun Li & Liwei Liu & Tianqi Lu & Yuhang Sui & Can Zhang & Yongwei Wang & Tao Zhang & Yu Xie & Peng Xiao & Zhongjie Zhao & Chundong Cheng & Jisheng Hu & Hongze Chen & Dongbo Xue & Hua Chen & Gang W, 2023. "Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    11. Katja Hartstock & Nadine A. Kueck & Petr Spacek & Anna Ovcharenko & Sabine Hüwel & Nicolas V. Cornelissen & Amarnath Bollu & Christoph Dieterich & Andrea Rentmeister, 2023. "MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Shu Zhang & Wen Fang & Siqi Zhou & Dongming Zhu & Ruidong Chen & Xin Gao & Zhuojin Li & Yao Fu & Yixuan Zhang & Fa Yang & Jing Zhao & Hao Wu & Pin Wang & Yonghua Shen & Shanshan Shen & Guifang Xu & Le, 2023. "Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    13. Cristina Leoni & Marian Bataclan & Taku Ito-Kureha & Vigo Heissmeyer & Silvia Monticelli, 2023. "The mRNA methyltransferase Mettl3 modulates cytokine mRNA stability and limits functional responses in mast cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    14. Kristin A. Fluke & Ryan T. Fuchs & Yueh-Lin Tsai & Victoria Talbott & Liam Elkins & Hallie P. Febvre & Nan Dai & Eric J. Wolf & Brett W. Burkhart & Jackson Schiltz & G. Brett Robb & Ivan R. Corrêa & T, 2024. "The extensive m5C epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    15. Elzbieta Kierzek & Xiaoju Zhang & Richard M. Watson & Scott D. Kennedy & Marta Szabat & Ryszard Kierzek & David H. Mathews, 2022. "Secondary structure prediction for RNA sequences including N6-methyladenosine," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    16. Debjit Khan & Iyappan Ramachandiran & Kommireddy Vasu & Arnab China & Krishnendu Khan & Fabio Cumbo & Dalia Halawani & Fulvia Terenzi & Isaac Zin & Briana Long & Gregory Costain & Susan Blaser & Amand, 2024. "Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m6A site accessibility," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    17. Marianna Ioannou & Dennis Hoving & Iker Valle Aramburu & Mia I. Temkin & Nathalia M. Vasconcelos & Theodora-Dorita Tsourouktsoglou & Qian Wang & Stefan Boeing & Robert Goldstone & Spyros Vernardis & V, 2022. "Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    18. Ting Wang & Yingli Zhou & Zilong Zhou & Pinggen Zhang & Ronghui Yan & Linchong Sun & Wenhao Ma & Tong Zhang & Shengqi Shen & Haiying Liu & Hui Lu & Ling Ye & Junru Feng & Zhaolin Chen & Xiuying Zhong , 2023. "Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Zhiyuan Luo & Qilian Ma & Shan Sun & Ningning Li & Hongfeng Wang & Zheng Ying & Shengdong Ke, 2023. "Exon-intron boundary inhibits m6A deposition, enabling m6A distribution hallmark, longer mRNA half-life and flexible protein coding," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Xiao-Lan Zhang & Xin-Hui Chen & Binwu Xu & Min Chen & Song Zhu & Nan Meng & Ji-Zhong Wang & Huifang Zhu & De Chen & Jin-Bao Liu & Guang-Rong Yan, 2023. "K235 acetylation couples with PSPC1 to regulate the m6A demethylation activity of ALKBH5 and tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-15, 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_s41467-023-44576-2. 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.