ArticleProceedings of the National Academy of Sciences of the United States of America2022
Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- An artificial intelligence optimized hepatic differentiation unveils NR5A2 and AP-1 transcriptional regulation in hepatic maturation.The Journal of biological chemistry · 2026Article
- Human iPSC-derived and conventional cancer models in precision oncology: advancing patient-specific therapies from bench to bedside.Journal of experimental & clinical cancer research : CR · 2026Review
- Alternative splicing in cancer drug resistance: Mechanisms and therapeutic prospects (Review).Oncology reports · 2026Review
- Engineering Mutation Clones in Mammalian Cells with CRISPR/Cas9.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Decoding cancer etiology with cellular reprogramming.Current opinion in genetics & development · 2025Review
- Circular RNAs and immunotherapy in retinoblastoma: emerging biomarkers and precision therapeutic strategies.Frontiers in immunology · 2025Review
- Osteosarcoma: A comprehensive review of model systems and experimental therapies.Medical research archives · 2024Article
- Molecular Biological Research on the Pathogenic Mechanism of Retinoblastoma.Current issues in molecular biology · 2024Review
- Heterozygous RB1 mutation enhanced ATP production in human iPSC-derived retinal organoids.Molecular biology reports · 2024Article
- Therapeutic Strategies for RB1-Deficient Cancers: Intersecting Gene Regulation and Targeted Therapy.Cancers · 2024Review
- Review
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- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis.iScience · 2023Article
- Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants.Cancer research · 2023Article
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Retinoblastoma gene expression profiling based on bioinformatics analysis.BMC medical genomics · 2023Article
- Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death.Cancer discovery · 2023Article
- Rewired mNature communications · 2023Article
- Hereditary cancer syndromes.World journal of clinical oncology · 2023Review
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated target responding to oncogenic stress in RB1-mutant cells. By investigating transcriptomes and genome occupancies in RB iPSC–derived osteoblasts (OBs), we discover that both E2F3a, which mediates spliceosomal gene expression, and pRB, which antagonizes E2F3a, coregulate more than one-third of spliceosomal genes by cobinding to their promoters or enhancers. Pharmacological inhibition of the spliceosome in RB1-mutant cells leads to global intron retention, decreased cell proliferation, and impaired tumorigenesis. Tumor specimen studies and genome-wide TCGA (The Cancer Genome Atlas) expression profile analyses support the clinical relevance of pRB and E2F3a in modulating spliceosomal gene expression in multiple cancer types including osteosarcoma (OS). High levels of pRB/E2F3a–regulated spliceosomal genes are associated with poor OS patient survival. Collectively, these findings reveal an undiscovered connection between pRB, E2F3a, the spliceosome, and tumorigenesis, pointing to the spliceosomal machinery as a potentially widespread therapeutic vulnerability of pRB-deficient cancers.
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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 OpenQuestion graph.