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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
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    References listed on IDEAS

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    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.
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