ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting PTBP3-Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Article
- Splicing-mediated control of hnRNPD isoform switching by SRSF2 drives PD-L1-dependent immune evasion in gallbladder cancer.Oncogene · 2026Article
- Cuproplasia-associated LOXL2 cooperates withJournal of gastrointestinal oncology · 2026Article
- SERPINE1 Alternative Polyadenylation Influences Gastric Cancer Prognosis via N6-Methyladenosine Modification.Cancer science · 2026Article
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- XRN2, governed by RNA-binding protein PTBP3, promotes the invasiveness of esophageal squamous cell carcinoma.Clinical & experimental metastasis · 2026Article
- Deconstructing cancer in 3D: models, mechanisms, and personalized solutions.Molecular cancer · 2026Review
- RNA splicing in cancer cell death regulation: shedding light on the molecular mechanisms and potential clinical applications.Cell death & disease · 2026Review
- Super-enhancer-driven LncRNA MIR205HG promotes esophageal squamous cell carcinoma progression via glycolysis reprogramming.Journal of translational medicine · 2026Article
- The role of alternative splicing in gastric cancer.Biology direct · 2026Review
- KDM5B-driven glucose metabolic reprogramming promotes enzalutamide resistance in prostate cancer via the lactate/hnRNPA1 lactylation/AR-V7 axis.Molecular cancer · 2026Article
- Role of cuproptosis in digestive system tumors (Review).International journal of molecular medicine · 2026Review
- Metabolic-Immune Reprogramming via CuZnS@BSA Nanoregulators to Overcome Resistance in Triple-Negative Breast Cancer.Theranostics · 2026Article
- A postoperative recurrence prediction model for intrahepatic cholangiocarcinoma based on multi-omics analysis of adjacent-to-tumor tissues.Frontiers in oncology · 2026Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Targeting ferroptosis and cuproptosis in gastrointestinal cancers: molecular mechanisms, metabolic vulnerabilities, and therapeutic interventions.Molecular biomedicine · 2025Review
- Targeting PTBP3-Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modeling the pre-metastatic niche of gastric cancer peritoneal metastasis under spatiotemporal resolution and investigating EVs-mediated immune suppression.Frontiers in immunology · 2025Review
- The role of cuproptosis in the occurrence and development of gastric cancer.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Numerous aberrant splicing events are implicated in tumor progression, yet comprehensive reports on splicing factors and events associated with peritoneal metastasis in gastric cancer (GCPM) are lacking. In this study, PTBP3 is found to be significantly overexpressed in peritoneal metastatic tissues of gastric cancer compared to primary tumor tissues, and higher PTBP3 expression correlates with poorer prognosis. Using gastric cancer cells and patient-derived organoids (PDO), the role of PTBP3 in promoting tumor invasion and proliferation is investigated. Mechanistically, through full-length transcriptome sequencing, PTBP3 mediates exon 4 skipping in its target gene COX11, leading to shorter transcripts that impair COX11 protein function, reducing mitochondrial copper content and enabling tumor cells to evade cuproptosis. Antisense oligonucleotide (ASO) drugs targeting the short COX11 transcripts effectively degrade mRNA, disrupting copper homeostasis. In PDO-based xenograft models, exogenous copper ionophores combined with ASO drugs induce excessive copper accumulation in mitochondria, triggering proteotoxic stress and cuproptosis. Overall, PTBP3-mediated exon 4 skipping in COX11 pre-mRNA is critical for tumor cell survival and progression in GCPM, offering potential therapeutic strategies targeting copper metabolism.
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