ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Hepatocyte Deletion of IGF2 Prevents DNA Damage and Tumor Formation in Hepatocellular Carcinoma.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- Vessels encapsulating tumor clusters is associated with impaired efficacy of adjuvant immunotherapy in resected hepatocellular carcinoma.Journal of advanced research · 2026Article
- Small nucleolar RNA host genes in hepatocellular carcinoma: an evidence-weighted and etiology-aware framework for mechanistic and translational interpretation.Molecular biology reports · 2026Review
- HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.Biomedicines · 2026Review
- Identification of a small-molecule targeting PLAGL2 DNA-binding domain inhibits extracellular matrix formation and enhances lenvatinib sensitivity in hepatocellular carcinoma.Acta pharmaceutica Sinica. B · 2026Article
- Let-7a and miR-34a Interplay Potent Suppressive Roles in Hepatocellular Carcinoma via Co-TargetingInternational journal of molecular sciences · 2026Article
- [Expression, Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Engineering Metal-Organic-Framework-Based STING Nanoagonists for PROTAC-Enhanced Cancer Chemo-Metalloimmunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglial TIA1-mediated stress granules promote neuroinflammation and aggravate neuron loss in mice after ischemic stroke by inhibiting IGF2 signaling.Theranostics · 2026Article
- Targeting MED23 inhibits hepatocellular carcinoma development by suppressing compensatory proliferation and facilitating ROS-mediated cell death.Cell death & disease · 2025Article
- RBM17 promotes hepatocellular carcinoma progression by regulating lipid metabolism and immune microenvironment: implications for therapeutic targeting.Cell death discovery · 2025Article
- Neutrophil-induced pyroptosis promotes survival in patients with hepatoblastoma.Cancer immunology, immunotherapy : CII · 2025Article
- B4GALNT1 Regulates Hepatocellular Carcinoma Cell Proliferation and Apoptosis via the PI3K-AKT-mTOR Pathway.Journal of clinical laboratory analysis · 2025Article
- Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma.Molecular cancer · 2025Article
- Mechanical stretch-induced IGF2 overexpression in epidermal keratinocytes promotes hypertrophic scar formation through the IGF1R/p-c-Jun axis.International journal of biological sciences · 2025Article
- Downregulated TRAF3IP2-AS1 promotes hepatocellular carcinoma progression through the miR-374a-5p/SEL1L1/RPL6 axis to enhance DNA damage repair.American journal of translational research · 2025Article
- BioinformaticsHeliyon · 2024Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Serine-arginine rich splicing factor 3 (SRSF3) plays a critical role in hepatocyte function and its loss in mice promotes chronic liver damage and leads to HCC. Hepatocyte-specific SRSF3 knockout mice (SKO mice) also overexpress insulin-like growth factor 2 (IGF2). In the present study, double deletion of Igf2 and Srsf3 (DKO mice) prevents hepatic fibrosis and inflammation, and completely prevents tumor formation, and is associated with decreased proliferation, apoptosis and DNA damage, and restored DNA repair enzyme expression. This is confirmed in vitro, where IGF2 treatment of HepG2 hepatoma cells decreases DNA repair enzyme expression and causes DNA damage. Tumors from the SKO mice also show mutational signatures consistent with homologous recombination and mismatch repair defects. Analysis of frozen human samples shows that SRSF3 protein is decreased sixfold in HCC compared to normal liver tissue but SRSF3 mRNA is increased. Looking at public TCGA data, HCC patients having high SRSF3 mRNA expression show poor survival, as do patients with alterations in known SRSF3-dependent splicing events. The results indicate that IGF2 overexpression in conjunction with reduced SRSF3 splicing activity could be a major cause of DNA damage and driver of liver cancer.
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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.