ArticleJournal of experimental & clinical cancer research : CR2022
ZNF498 promotes hepatocellular carcinogenesis by suppressing p53-mediated apoptosis and ferroptosis via the attenuation of p53 Ser46 phosphorylation.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Review
- Single-cell analysis reveals an endothelial TP53-CXCL14 axis in breast cancer progression.Journal of translational medicine · 2026Article
- KRAB Zinc-Finger Protein ZNF205 Promotes Hepatocellular Carcinoma via p53 Pathway Repression.Cancer science · 2026Article
- LncRNA EGFR-AS1 inhibits ferroptosis to reduce radiosensitivity of cervical cancer through the m6A/IGF2BP3/APAF1 axis.BMC cancer · 2026Article
- Zinc finger proteins (ZFPs) in health and disease.Molecular biomedicine · 2026Review
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- Itraconazole induced ferroptosis in acute myeloid leukemia cells through TP53INP1.Frontiers in molecular biosciences · 2026Article
- The promising arsenal of ferroptosis inducers in bladder cancer.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Ferroptosis: biology and role in liver disease.Journal of gastroenterology · 2025Review
- Multi-omics whole-genome characterization of the copy number landscape of metastatic pancreatic ductal adenocarcinoma.iScience · 2025Article
- The Regulation of Trace Metal Elements in Cancer Ferroptosis.Advanced biology · 2025Review
- tsRNA, cell death and disease: Connecting the dots.Non-coding RNA research · 2025Review
- HCV-related hepatocellular carcinoma: gene signatures associated with TERT promoter mutations and sex.Journal of translational medicine · 2025Article
- Unraveling the complex role of tumor-associated neutrophils within solid tumors.Cancer immunology, immunotherapy : CII · 2025Review
- DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.Proteomes · 2025Article
- Ferroptosis: insight into the treatment of hepatocellular carcinoma.Cancer cell international · 2024Review
- Ferroptosis: a new promising target for hepatocellular carcinoma therapy.Molecular and cellular biochemistry · 2024Review
- ZNF8 Orchestrates with Smad3 to Promote Lung Metastasis by Recruiting SMYD3 in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer.World journal of gastrointestinal oncology · 2024Review
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundDysfunctional p53 signaling is one of the major causes of hepatocellular carcinoma (HCC) tumorigenesis and development, but the mechanisms underlying p53 inactivation in HCC have not been fully clarified. The role of Krüppel-associated box (KRAB)-type zinc-finger protein ZNF498 in tumorigenesis and the underlying mechanisms are poorly understood.
methodsClinical HCC samples were used to assess the association of ZNF498 expression with clinicopathological characteristics and patient outcomes. A mouse model in which HCC was induced by diethylnitrosamine (DEN) was used to explore the role of ZNF498 in HCC initiation and progression. ZNF498 overexpression and knockdown HCC cell lines were employed to examine the effects of ZNF498 on cellular proliferation, apoptosis, ferroptosis and tumor growth. Western blotting, immunoprecipitation, qPCR, luciferase assays and flow cytometry were also conducted to determine the underlying mechanisms related to ZNF498 function.
resultsZNF498 was found to be highly expressed in HCC, and increased ZNF498 expression was positively correlated with advanced pathological grade and poor survival in HCC patients. Furthermore, ZNF498 promoted DEN-induced hepatocarcinogenesis and progression in mice. Mechanistically, ZNF498 directly interacted with p53 and suppressed p53 transcriptional activation by inhibiting p53 Ser46 phosphorylation. ZNF498 competed with p53INP1 for p53 binding and suppressed PKCδ- and p53INP1-mediated p53 Ser46 phosphorylation. In addition, functional assays revealed that ZNF498 promoted liver cancer cell growth in vivo and in vitro in a p53-dependent manner. Moreover, ZNF498 inhibited p53-mediated apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation.
conclusionsOur results strongly suggest that ZNF498 suppresses apoptosis and ferroptosis by attenuating p53 Ser46 phosphorylation in hepatocellular carcinogenesis, revealing a novel ZNF498-PKCδ-p53INP1-p53 axis in HCC cells that would enrich the non-mutation p53-inactivating mechanisms in HCC.
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