ArticleMolecular cancer2012
IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors.
Article in Molecular cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 53 citations in OpenAlex.
- IGFBP3 As a Potential Biomarker and Therapeutic Target in Hepatocellular Carcinoma: A Multi-Cohort Analysis.Journal of clinical laboratory analysis · 2026Article
- Insulin-like growth factor binding protein-3 serves as a biomarker for resistance to enzalutamide in prostate cancer.Apoptosis : an international journal on programmed cell death · 2026Article
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- Hepatoblastoma.Nature reviews. Disease primers · 2025Review
- Hepatoblastoma: From Molecular Mechanisms to Therapeutic Strategies.Current oncology (Toronto, Ont.) · 2025Review
- Metabolic and Epigenetic Mechanisms in Hepatoblastoma: Insights into Tumor Biology and Therapeutic Targets.Genes · 2024Review
- Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma.Hepatology communications · 2024Article
- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- RNA N6-methyladenosine reader IGF2BP3 interacts with MYCN and facilitates neuroblastoma cell proliferation.Cell death discovery · 2023Article
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- Serum insulin-like growth factor binding protein 3 as a promising diagnostic and prognostic biomarker in esophagogastric junction adenocarcinoma.Discover oncology · 2022Article
- The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance.International journal of molecular sciences · 2021Review
- Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver MetastasisFrontiers in oncology · 2021Article
- The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia.Frontiers in cell and developmental biology · 2021Review
- Molecular Mechanisms of Hepatoblastoma.Seminars in liver disease · 2021Article
- DNA methylation in Hepatoblastoma-a literature review.Italian journal of pediatrics · 2020Review
- HBprem: A database of transcription, translation, and posttranscriptional and posttranslational modifications in hepatoblastoma.Clinical and translational medicine · 2020Article
- GIPC-Regulated IGFBP-3 Promotes HSC Migration In Vitro and Portal Hypertension In Vivo Through a β1-Integrin Pathway.Cellular and molecular gastroenterology and hepatology · 2020Article
- Review
- Upregulation of long non-coding RNA FOXP4-AS1 and its regulatory network in hepatocellular carcinoma.OncoTargets and therapy · 2019Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 (IGF2), loss of imprinting at the IGF2/H19 locus, and amplification of pleomorphic adenoma gene 1 (PLAG1) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers.
resultsThe IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion.
conclusionThis study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.
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