ArticleThe EMBO journal2024
Alternative splicing of PBRM1 mediates resistance to PD-1 blockade therapy in renal cancer.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- MASQ: Toward clinical quantification of disease-associated alternative splicing.Molecular therapy. Nucleic acids · 2026Article
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- MASQ: A multiplex qPCR platform for quantitative alternative splicing analysis in clinical specimens.Molecular therapy. Nucleic acids · 2026Article
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Article
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- Single-Cell and Machine Learning Analyses Identify MYDGF as an Immune-Related Biomarker Associated With the Tumor Microenvironment in Clear Cell Renal Cell Carcinoma.Human mutation · 2026Article
- Alternative splicing of KRAS exon 4 promotes tumor progression via enhanced KRAS4A oncogenic activity.Animal cells and systems · 2026Article
- mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025Review
- The fall of the genome protectors triad: PBRM1, SETD2, and BAP1's impact on metabolism and immunity in clear cell renal cell carcinoma.Frontiers in cell and developmental biology · 2025Review
- Comprehensive analysis of metabolic patterns in renal cell carcinoma: implications for prognosis and treatment.Frontiers in immunology · 2025Article
- Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma.Frontiers in immunology · 2025Article
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Alternative pre-mRNA splicing (AS) is a biological process that results in proteomic diversity. However, implications of AS alterations in cancer remain poorly understood. Herein, we performed a comprehensive AS analysis in cancer driver gene transcripts across fifteen cancer types and found global alterations in inclusion rates of the PBAF SWI/SNF chromatin remodeling complex subunit Polybromo 1 (PBRM1) exon 27 (E27) in most types of cancer tissues compared with those in normal tissues. Further analysis confirmed that PBRM1 E27 is excluded by the direct binding of RBFOX2 to intronic UGCAUG elements. In addition, the E27-included PBRM1 isoform upregulated PD-L1 expression via enhanced PBAF complex recruitment to the PD-L1 promoter. PBRM1 wild-type patients with clear cell renal cell carcinoma were resistant to PD-1 blockade therapy when they expressed low RBFOX2 mRNA levels. Overall, our study suggests targeting of RBFOX2-mediated AS of PBRM1 as a potential therapeutic strategy for immune checkpoint blockade.
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Registered trials
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