IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37542-5.html
   My bibliography  Save this article

PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer

Author

Listed:
  • Yunxing Shi

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Yi Niu

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Yichuan Yuan

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Kai Li

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Chengrui Zhong

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Zhiyu Qiu

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Keren Li

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Zhu Lin

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Zhiwen Yang

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Dinglan Zuo

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Jiliang Qiu

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Wei He

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Chenwei Wang

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Yadi Liao

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine)

  • Guocan Wang

    (The University of Texas MD Anderson Cancer Center)

  • Yunfei Yuan

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

  • Binkui Li

    (State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine
    Sun Yat-Sen University Cancer Center)

Abstract

Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clinic. Through functional screening using CRISPR/Cas9 activation library, transcriptomic profiling of clinical samples, and functional validation in vitro and in vivo, we identify PRMT3 as a key driver of oxaliplatin resistance. Mechanistically, PRMT3-mediated oxaliplatin-resistance is in part dependent on the methylation of IGF2BP1 at R452, which is critical for the function of IGF2BP1 in stabilizing the mRNA of HEG1, an effector of PRMT3-IGF2BP1 axis. Also, PRMT3 overexpression may serve as a biomarker for oxaliplatin resistance in HCC patients. Collectively, our study defines the PRTM3-IGF2BP1-HEG1 axis as important regulators and therapeutic targets in oxaliplatin-resistance and suggests the potential to use PRMT3 expression level in pretreatment biopsy as a biomarker for oxaliplatin-resistance in HCC patients.

Suggested Citation

  • Yunxing Shi & Yi Niu & Yichuan Yuan & Kai Li & Chengrui Zhong & Zhiyu Qiu & Keren Li & Zhu Lin & Zhiwen Yang & Dinglan Zuo & Jiliang Qiu & Wei He & Chenwei Wang & Yadi Liao & Guocan Wang & Yunfei Yuan, 2023. "PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37542-5
    DOI: 10.1038/s41467-023-37542-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37542-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37542-5?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. Lei Huang & Xiao-Ou Zhang & Esteban J. Rozen & Xiaomei Sun & Benjamin Sallis & Odette Verdejo-Torres & Kim Wigglesworth & Daniel Moon & Tingting Huang & John P. Cavaretta & Gang Wang & Lei Zhang & Jas, 2022. "PRMT5 activates AKT via methylation to promote tumor metastasis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Silvana Konermann & Mark D. Brigham & Alexandro E. Trevino & Julia Joung & Omar O. Abudayyeh & Clea Barcena & Patrick D. Hsu & Naomi Habib & Jonathan S. Gootenberg & Hiroshi Nishimasu & Osamu Nureki &, 2015. "Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex," Nature, Nature, vol. 517(7536), pages 583-588, January.
    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. Tian Zhou & Xinyi Zhu & Zhizhong Ye & Yong-Fei Wang & Chao Yao & Ning Xu & Mi Zhou & Jianyang Ma & Yuting Qin & Yiwei Shen & Yuanjia Tang & Zhihua Yin & Hong Xu & Yutong Zhang & Xiaoli Zang & Huihua D, 2022. "Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Shaela Wright & Xujie Zhao & Wojciech Rosikiewicz & Shelby Mryncza & Judith Hyle & Wenjie Qi & Zhenling Liu & Siqi Yi & Yong Cheng & Beisi Xu & Chunliang Li, 2023. "Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Haipeng Fu & Tingyu Wang & Xiaohui Kong & Kun Yan & Yang Yang & Jingyi Cao & Yafei Yuan & Nan Wang & Kehkooi Kee & Zhi John Lu & Qiaoran Xi, 2022. "A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Heathcliff Dorado García & Fabian Pusch & Yi Bei & Jennifer Stebut & Glorymar Ibáñez & Kristina Guillan & Koshi Imami & Dennis Gürgen & Jana Rolff & Konstantin Helmsauer & Stephanie Meyer-Liesener & N, 2022. "Therapeutic targeting of ATR in alveolar rhabdomyosarcoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Yafeng Wang & Guiquan Zhang & Qingzhou Meng & Shisheng Huang & Panpan Guo & Qibin Leng & Lingyun Sun & Geng Liu & Xingxu Huang & Jianghuai Liu, 2022. "Precise tumor immune rewiring via synthetic CRISPRa circuits gated by concurrent gain/loss of transcription factors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Tiantian Jing & Dianhui Wei & Xiaoli Xu & Chengsi Wu & Lili Yuan & Yiwen Huang & Yizhen Liu & Yanyi Jiang & Boshi Wang, 2024. "Transposable elements-mediated recruitment of KDM1A epigenetically silences HNF4A expression to promote hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    8. Xiangfeng Kong & Hainan Zhang & Guoling Li & Zikang Wang & Xuqiang Kong & Lecong Wang & Mingxing Xue & Weihong Zhang & Yao Wang & Jiajia Lin & Jingxing Zhou & Xiaowen Shen & Yinghui Wei & Na Zhong & W, 2023. "Engineered CRISPR-OsCas12f1 and RhCas12f1 with robust activities and expanded target range for genome editing," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    10. Deqiang Kong & Yang Zhou & Yu Wei & Xinyi Wang & Qin Huang & Xianyun Gao & Hang Wan & Mengyao Liu & Liping Kang & Guiling Yu & Jianli Yin & Ningzi Guan & Haifeng Ye, 2024. "Exploring plant-derived phytochrome chaperone proteins for light-switchable transcriptional regulation in mammals," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Anna Gogleva & Dimitris Polychronopoulos & Matthias Pfeifer & Vladimir Poroshin & Michaël Ughetto & Matthew J. Martin & Hannah Thorpe & Aurelie Bornot & Paul D. Smith & Ben Sidders & Jonathan R. Dry &, 2022. "Knowledge graph-based recommendation framework identifies drivers of resistance in EGFR mutant non-small cell lung cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. Rui Chen & Xinyao Shi & Xiangrui Yao & Tong Gao & Guangyu Huang & Duo Ning & Zemin Cao & Youxin Xu & Weizheng Liang & Simon Zhongyuan Tian & Qionghua Zhu & Liang Fang & Meizhen Zheng & Yuhui Hu & Huan, 2024. "Specific multivalent molecules boost CRISPR-mediated transcriptional activation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. 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.
    15. Amy J. Heidersbach & Kristel M. Dorighi & Javier A. Gomez & Ashley M. Jacobi & Benjamin Haley, 2023. "A versatile, high-efficiency platform for CRISPR-based gene activation," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    16. Xuemei Bai & Chao Sui & Feng Liu & Tian Chen & Lei Zhang & Yi Zheng & Bingyu Liu & Chengjiang Gao, 2022. "The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Yexuan Deng & Sarah T. Diepstraten & Margaret A. Potts & Göknur Giner & Stephanie Trezise & Ashley P. Ng & Gerry Healey & Serena R. Kane & Amali Cooray & Kira Behrens & Amy Heidersbach & Andrew J. Kue, 2022. "Generation of a CRISPR activation mouse that enables modelling of aggressive lymphoma and interrogation of venetoclax resistance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    18. Arpiar Saunders & Kee Wui Huang & Cassandra Vondrak & Christina Hughes & Karina Smolyar & Harsha Sen & Adrienne C. Philson & James Nemesh & Alec Wysoker & Seva Kashin & Bernardo L. Sabatini & Steven A, 2022. "Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    19. Zhongxuan Zhang & Xiaoxiao Rong & Tianjin Xie & Zehao Li & Haozhi Song & Shujun Zhen & Haifeng Wang & Jiahui Wu & Samie R. Jaffrey & Xing Li, 2024. "Fluorogenic CRISPR for genomic DNA imaging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    20. Wing Fuk Chan & Hannah D. Coughlan & Yunshun Chen & Christine R. Keenan & Gordon K. Smyth & Andrew C. Perkins & Timothy M. Johanson & Rhys S. Allan, 2022. "Activation of stably silenced genes by recruitment of a synthetic de-methylating module," Nature Communications, Nature, vol. 13(1), pages 1-9, 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:14:y:2023:i:1:d:10.1038_s41467-023-37542-5. 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.