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journal article·2025-06Open access

PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma

Shixian Liu, Wentao Zhang, Weiwei Liu, Zhao Ding, Ruijing Zhang, Yuefeng Han, Zihao Niu, Mengdie Zhang, Hui Li, Dapeng Li, Zixi Wang, Jie Peng, Yu Wu, Yanxun Han, Zihui Xie, Jing Wu, Liang Qin, Zhongdong Hu, Xu Chen, Yunlong Hu, Yehai Liu, Shiyin Ma, Xiaojun Zha

Advanced Science· Volume 12· Issue 22
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Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is a malignancy with poor prognosis and chemotherapy resistance. Here, protein arginine methyltransferase 1 (PRMT1) is identified as a key driver of carboplatin (CBP) resistance in HNSCC. Analyses of clinical samples, cell lines, patient‐derived organoids, and xenograft models reveal that PRMT1 promotes tumor growth and CBP resistance through a novel, methyltransferase‐independent mechanism. Conditional PRMT1 knockout suppresses tumorigenesis and enhances CBP sensitivity in vivo, highlighting its essential role in HNSCC progression. Mechanistically, PRMT1 recruits the SWI/SNF chromatin remodeling complex via direct interaction with SMARCC1, leading to the transcriptional activation of insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2), which enhances CBP resistance and tumor growth. Notably, this function is independent of PRMT1's enzymatic activity, distinguishing it from its well‐established roles in arginine methylation. Furthermore, pre‐B‐cell leukemia homeobox 2 (PBX2) is identified as an upstream transcriptional activator that binds the PRMT1 promoter, driving its overexpression and reinforcing this oncogenic network. Clinically, high PBX2, PRMT1, SMARCC1, and IGF2BP2 expression correlates with malignant progression and poor prognosis in HNSCC patients. This study uncovers a previously unrecognized non‐catalytic function of PRMT1 and highlights the PBX2‐PRMT1‐SWI/SNF‐IGF2BP2 axis as a potential therapeutic target for overcoming CBP resistance in HNSCC.
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Research context

CompositesCatalysis & surfaces

OpenAlex topics: Cancer-related gene regulation · Epigenetics and DNA Methylation · RNA modifications and cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 China

Department of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 China

Department of Biochemistry & Molecular Biology School of Basic Medicine Anhui Medical University Hefei 230032 China

Department of Otolaryngology Head and Neck Surgery and Scientific Research and Experiment Center The Affiliated Bozhou Hospital of Anhui Medical University Bozhou 236800 China

Institutes of Biomedical Sciences Children's Hospital of Fudan University National Children's Medical Center Fudan University Shanghai 200032 China

Department of Urology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 China

Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese Medicine Beijing University of Chinese Medicine Beijing 100029 China

Department of Otolaryngology Head and Neck Surgery Anhui NO.2 Provincial People's Hospital Hefei 230041 China

Funding

Innovative Research Group Project of the National Natural Science Foundation of China · Natural Science Foundation of Anhui Province · Anhui Medical University · University Natural Science Research Project of Anhui Province

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