ArticleProceedings of the National Academy of Sciences of the United States of America2020
Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Analysing Differential Alternative Splicing Events and Their Impact on Retinoblastoma Progression Using RNA-seq Metadata.Asian Pacific journal of cancer prevention : APJCP · 2025Pooled it
- The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches.Prostate cancer and prostatic diseases · 2022Pooled it
- Mechanisms of LARP7 in regulating the progression of non-small cell lung cancer.Journal of thoracic disease · 2026Article
- Global landscape of protein-coding and long non-coding RNA alternative splicing and regulation in the human esophageal squamous cell carcinoma.Cancer cell international · 2026Article
- Saikosaponin‑D triggers cancer cell death by targeting the PIM1/c-Myc axis to reprogram oncogenic alternative splicing.Cell death discovery · 2025Article
- SpliceDecoder: A High-Throughput Tool for Guiding the Functional Interpretation of Differential Splicing Events.bioRxiv : the preprint server for biology · 2025Article
- Article
- Transcriptomic signatures of prostate cancer progression: a comprehensive RNA-seq study.3 Biotech · 2025Article
- Antisense oligonucleotide-mediated TRA2β poison exon inclusion induces the expression of a lncRNA with anti-tumor effects.Nature communications · 2025Article
- The role of chromatin state in intron retention: A case study in leveraging large scale deep learning models.PLoS computational biology · 2025Article
- Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.Molecular therapy. Oncology · 2024Article
- CancerPro: deciphering the pan-cancer prognostic landscape through combinatorial enrichment analysis and knowledge network insights.NAR genomics and bioinformatics · 2024Article
- Targeting IRE1α reprograms the tumor microenvironment and enhances anti-tumor immunity in prostate cancer.Nature communications · 2024Article
- PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression.Genome medicine · 2024Article
- Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation.EMBO reports · 2024Article
- Review
- rMATS-turbo: an efficient and flexible computational tool for alternative splicing analysis of large-scale RNA-seq data.Nature protocols · 2024Review
- Article
- Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
We sought to define the landscape of alternative pre-mRNA splicing in prostate cancers and the relationship of exon choice to known cancer driver alterations. To do so, we compiled a metadataset composed of 876 RNA-sequencing (RNA-Seq) samples from five publicly available sources representing a range of prostate phenotypes from normal tissue to drug-resistant metastases. We subjected these samples to exon-level analysis with rMATS-turbo, purpose-built software designed for large-scale analyses of splicing, and identified 13,149 high-confidence cassette exon events with variable incorporation across samples. We then developed a computational framework, pathway enrichment-guided activity study of alternative splicing (PEGASAS), to correlate transcriptional signatures of 50 different cancer driver pathways with these alternative splicing events. We discovered that Myc signaling was correlated with incorporation of a set of 1,039 cassette exons enriched in genes encoding RNA binding proteins. Using a human prostate epithelial transformation assay, we confirmed the Myc regulation of 147 of these exons, many of which introduced frameshifts or encoded premature stop codons. Our results connect changes in alternative pre-mRNA splicing to oncogenic alterations common in prostate and many other cancers. We also establish a role for Myc in regulating RNA splicing by controlling the incorporation of nonsense-mediated decay-determinant exons in genes encoding RNA binding proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.