PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma DOI Creative Commons
Shixian Liu, Wentao Zhang, Weiwei Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

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

Language: Английский

PRMT1‐Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma DOI Creative Commons
Shixian Liu, Wentao Zhang, Weiwei Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

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

Language: Английский

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