ArticleCellular and molecular gastroenterology and hepatology2021
HDAC1-Dependent Repression of Markers of Hepatocytes and P21 Is Involved in Development of Pediatric Liver Cancer.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 32 citations in OpenAlex.
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- Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.Journal of virology · 2025Article
- The Role of Chronic Inflammation in Pediatric Cancer.Cancers · 2025Review
- DNAJB1-PKAc Kinase Is Expressed in Young Patients with Pediatric Liver Cancers and Enhances Carcinogenic Pathways.Cancers · 2024Article
- LINC01094 promotes gastric cancer through dual targeting of CDKN1A by directly binding RBMS2 and HDAC1.Biology direct · 2024Article
- Metabolic and Epigenetic Mechanisms in Hepatoblastoma: Insights into Tumor Biology and Therapeutic Targets.Genes · 2024Review
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- Cellular origin and molecular mechanisms of lung metastases in patients with aggressive hepatoblastoma.Hepatology communications · 2024Article
- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- DNA damage repair-related gene signature for identifying the immune status and predicting the prognosis of hepatocellular carcinoma.Scientific reports · 2023Article
- ZFP64 Promotes Gallbladder Cancer Progression through Recruiting HDAC1 to Activate NOTCH1 Signaling Pathway.Cancers · 2023Article
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- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
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- Network pharmacology andFrontiers in pharmacology · 2022Article
- The Potential Mechanism of HDAC1-Catalyzed Histone Crotonylation of Caspase-1 in Nonsmall Cell Lung Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022Article
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12 authors at 3 institutions in 2 countries.
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Abstract
BACKGROUND &
aimsEpigenetic regulation of gene expression plays a critical role in the development of liver cancer; however, the molecular mechanisms of epigenetic-driven liver cancers are not well understood. The aims of this study were to examine molecular mechanisms that cause the dedifferentiation of hepatocytes into cancer cells in aggressive hepatoblastoma and test if the inhibition of these mechanisms inhibits tumor growth.
methodsWe have analyzed CCAAT/Enhancer Binding Protein alpha (C/EBPα), Transcription factor Sp5, and histone deacetylase (HDAC)1 pathways from a large biobank of fresh hepatoblastoma (HBL) samples using high-pressure liquid chromatography-based examination of protein-protein complexes and have examined chromatin remodeling on the promoters of markers of hepatocytes and p21. The HDAC1 activity was inhibited in patient-derived xenograft models of HBL and in cultured hepatoblastoma cells and expression of HDAC1-dependent markers of hepatocytes was examined.
resultsAnalyses of a biobank showed that a significant portion of HBL patients have increased levels of an oncogenic de-phosphorylated-S190-C/EBPα, Sp5, and HDAC1 compared with amounts of these proteins in adjacent regions. We found that the oncogenic de-phosphorylated-S190-C/EBPα is created in aggressive HBL by protein phosphatase 2A, which is increased within the nucleus and dephosphorylates C/EBPα at Ser190. C/EBPα-HDAC1 and Sp5-HDAC1 complexes are abundant in hepatocytes, which dedifferentiate into cancer cells. Studies in HBL cells have shown that C/EBPα-HDAC1 and Sp5-HDAC1 complexes reduce markers of hepatocytes and p21 via repression of their promoters. Pharmacologic inhibition of C/EBPα-HDAC1 and Sp5-HDAC1 complexes by Suberoylanilide hydroxamic acid (SAHA) and small interfering RNA-mediated inhibition of HDAC1 increase expression of hepatocyte markers, p21, and inhibit proliferation of cancer cells.
conclusionsHDAC1-mediated repression of markers of hepatocytes is an essential step for the development of HBL, providing background for generation of therapies for aggressive HBL by targeting HDAC1 activities.
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