PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma
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...
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Wiley
2025-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202417460 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shixian Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8098e978f8fe489988fb33c0ae37d8ec |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8098e978f8fe489988fb33c0ae37d8ec2025-08-20T03:44:51ZengWileyAdvanced Science2198-38442025-06-011222n/an/a10.1002/advs.202417460PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell CarcinomaShixian Liu0Wentao Zhang1Weiwei Liu2Zhao Ding3Ruijing Zhang4Yuefeng Han5Zihao Niu6Mengdie Zhang7Hui Li8Dapeng Li9Zixi Wang10Jie Peng11Yu Wu12Yanxun Han13Zihui Xie14Jing Wu15Liang Qin16Zhongdong Hu17Xu Chen18Yunlong Hu19Yehai Liu20Shiyin Ma21Xiaojun Zha22Department of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Otolaryngology Head and Neck Surgery and Scientific Research and Experiment Center The Affiliated Bozhou Hospital of Anhui Medical University Bozhou 236800 ChinaDepartment of Biochemistry & Molecular Biology School of Basic Medicine Anhui Medical University Hefei 230032 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Urology Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200080 ChinaModern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese Medicine Beijing University of Chinese Medicine Beijing 100029 ChinaDepartment of Biochemistry & Molecular Biology School of Basic Medicine Anhui Medical University Hefei 230032 ChinaDepartment of Otolaryngology Head and Neck Surgery Anhui NO.2 Provincial People's Hospital Hefei 230041 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Anhui Medical University Hefei 230022 ChinaDepartment of Otolaryngology Head & Neck Surgery The First Affiliated Hospital of Bengbu Medical University Bengbu 233004 ChinaDepartment of Biochemistry & Molecular Biology School of Basic Medicine Anhui Medical University Hefei 230032 ChinaAbstract 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.https://doi.org/10.1002/advs.202417460chemoresistanceHNSCCIGF2BP2PRMT1SWI/SNF Complex |
| spellingShingle | 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 PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma Advanced Science chemoresistance HNSCC IGF2BP2 PRMT1 SWI/SNF Complex |
| title | PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma |
| title_full | PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma |
| title_fullStr | PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma |
| title_short | PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma |
| title_sort | prmt1 mediated swi snf complex recruitment via smarcc1 drives igf2bp2 transcription to enhance carboplatin resistance in head and neck squamous cell carcinoma |
| topic | chemoresistance HNSCC IGF2BP2 PRMT1 SWI/SNF Complex |
| url | https://doi.org/10.1002/advs.202417460 |
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