ArticleHepatology (Baltimore, Md.)2015
Deletion of serine/arginine-rich splicing factor 3 in hepatocytes predisposes to hepatocellular carcinoma in mice.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 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
- The RNA-binding protein SRSF3 controls epicardial formation by regulating splicing and proliferation.Development (Cambridge, England) · 2026Article
- Inhibition of the U12-type splicing factor ZCRB1 mediates retention of the USP21 minor intron to suppress malignant progression in hepatocellular carcinoma.Hepatology international · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Isoforms in action: The impact of transcript diversity in phenotype.Genetics and molecular biology · 2026Article
- LL22NC03-N14H11.1 regulates the m6A modification of MYC and promotes glycolytic activity in hepatocellular carcinoma cells by inhibiting IGF2BP3 ubiquitination degradation.Journal of experimental & clinical cancer research : CR · 2025Article
- Bioinformatics frameworks for single-cell long-read sequencing: unlocking isoform-level resolution.Briefings in bioinformatics · 2025Review
- Transcriptome alterations underlying metabolic dysfunction and liver disease in myotonic dystrophy type 1.Human molecular genetics · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- Exploring RNA biology in pseudomyxoma peritonei uncovers splicing dysregulation as a novel, targetable molecular vulnerability.Cancer gene therapy · 2025Article
- PPM1G and its diagnostic, prognostic and therapeutic potential in HCC (Review).International journal of oncology · 2024Review
- Targeting SNRNP200-induced splicing dysregulation offers an immunotherapy opportunity for glycolytic triple-negative breast cancer.Cell discovery · 2024Article
- Review
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- DCDC2 inhibits hepatic stellate cell activation and ameliorates CClScientific reports · 2024Article
- Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Insulin receptor alternative splicing in breast and prostate cancer.Cancer cell international · 2024Review
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledAlterations in RNA splicing are associated with cancer, but it is not clear whether they result from malignant transformation or have a causative role. We show here that hepatocyte-specific deletion of serine/arginine-rich splicing factor 3 (SRSF3) impairs hepatocyte maturation and metabolism in early adult life, and mice develop spontaneous hepatocellular carcinoma (HCC) with aging. Tumor development is preceded by chronic liver disease with progressive steatosis and fibrosis. SRSF3 protects mice against CCl4 -induced fibrosis and carcinogenesis and suppresses inclusion of the profibrogenic EDA exon in fibronectin 1. Loss of SRSF3 increases expression of insulin-like growth factor 2 and the A-isoform of the insulin receptor, allowing aberrant activation of mitogenic signaling, promotes aberrant splicing and expression of epithelial to mesenchymal transition (EMT) genes, and activates Wnt/β-catenin signaling leading to c-Myc induction. Finally, SRSF3 expression is either decreased or the protein mislocalized in human HCC.
conclusionOur data suggest a potential role for SRSF3 in preventing hepatic carcinogenesis by regulating splicing to suppress fibrosis, mitogenic splicing, and EMT. Thus, these mice may provide an attractive model to discover the pathogenic mechanisms linking aberrant pre-messenger RNA splicing with liver damage, fibrosis, and HCC.
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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.