PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma
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.
Authors
- Hui Li (ORCID: https://orcid.org/0000-0001-7145-4681)
- Zhongdong Hu (ORCID: https://orcid.org/0000-0003-4849-3353)
- Wentao Zhang
- Yanxun Han (ORCID: https://orcid.org/0009-0003-6412-2568)
- Yuefeng Han (ORCID: https://orcid.org/0000-0002-1277-6207)
- Yehai Liu (ORCID: https://orcid.org/0000-0003-3977-2481)
- Ruijing Zhang (ORCID: https://orcid.org/0000-0002-0044-1573)
- Mengdie Zhang (ORCID: https://orcid.org/0009-0003-5176-2013)
- Jing Wu (ORCID: https://orcid.org/0000-0002-0756-7304)
- Zongling Niu (ORCID: https://orcid.org/0009-0006-4193-2076)
- Yunlong Hu (ORCID: https://orcid.org/0000-0003-4837-3941)
- Xiaojun Zha (ORCID: https://orcid.org/0000-0003-4006-0748)
- Weiwei Liu (ORCID: https://orcid.org/0000-0001-6036-9641)
- Jianfeng Zhang (ORCID: https://orcid.org/0000-0002-4240-0657)
- Dapeng Li (ORCID: https://orcid.org/0000-0003-0571-5876)
- Xu Chen (ORCID: https://orcid.org/0009-0007-1048-9507)
- Zixi Wang (ORCID: https://orcid.org/0000-0001-8828-4228)
- Shiyin Ma (ORCID: https://orcid.org/0000-0001-6867-7200)
- Jie Peng (ORCID: https://orcid.org/0000-0002-8733-3750)
- Ding Zhao (ORCID: https://orcid.org/0009-0008-2290-8921)
- Shixian Liu (ORCID: https://orcid.org/0000-0003-1445-4057)
- Liang Qin
- Zihui Xie
Institutions
- Beijing University of Chinese Medicine (CN)
- Shanghai Jiao Tong University (CN)
- Anhui Medical University (CN)
- Bozhou People's Hospital (CN)
- Anhui Provincial Hospital (CN)
- Shanghai First People's Hospital (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
- First Affiliated Hospital of Bengbu Medical College (CN)
- Children's Hospital of Fudan University (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1002/advs.202417460
- Citations
- 3
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Innovative Research Group Project of the National Natural Science Foundation of China
- Anhui Medical University
- Natural Science Foundation of Anhui Province
- University Natural Science Research Project of Anhui Province