ArticleEBioMedicine2020
ZHX2 restricts hepatocellular carcinoma by suppressing stem cell-like traits through KDM2A-mediated H3K36 demethylation.
Article in EBioMedicine, 2020. 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, 97 citations in OpenAlex.
- Kdm2a histone demethylase ablation restores anti-tumor immunogenicity in liver cancer.British journal of cancer · 2026Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Identification and validation of a ferroptosis-related long non-coding RNA signature as a prognostic biomarker for hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Emerging artificial intelligence-driven precision therapies in tumor drug resistance: recent advances, opportunities, and challenges.Molecular cancer · 2025Review
- Aquaporin 9 downregulation in KRASScientific reports · 2025Article
- Review
- Targeted silencing of SOCS1 by DNMT1 promotes stemness of human liver cancer stem-like cells.Cancer cell international · 2024Article
- The Unique Role of the Second Coordination Sphere to Unlock and Control Catalysis in Nonheme Fe(II)/2-Oxoglutarate Histone Demethylase KDM2A.Inorganic chemistry · 2024Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- LINC00942 inhibits ferroptosis and induces the immunosuppression of regulatory T cells by recruiting IGF2BP3/SLC7A11 in hepatocellular carcinoma.Functional & integrative genomics · 2024Article
- Research Progress on the Role of Epigenetic Methylation Modification in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 2023Article
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- HSP90, as a functional target antigen of a mAb 11C9, promotes stemness and tumor progression in hepatocellular carcinoma.Stem cell research & therapy · 2023Article
- Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.Cell death and differentiation · 2023Article
- Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis.Cell death discovery · 2023Article
- Cancer stem cell fate determination: mito-nuclear communication.Cell communication and signaling : CCS · 2023Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLiver cancer stem cells (CSCs) are critical determinants of HCC relapse and therapeutic resistance, but the mechanisms underlying the maintenance of CSCs are poorly understood. We aimed to explore the role of tumor repressor Zinc-fingers and homeoboxes 2 (ZHX2) in liver CSCs.
methodsCD133
resultsZHX2 expression was significantly reduced in liver CSCs from different origins. ZHX2 deficiency led to enhanced liver tumor progression and expansion of CSC populations in vitro and in vivo. Re-expression of ZHX2 restricted capabilities of hepatic CSCs in supporting tumor initiation, self-renewal and sorafenib-resistance. Mechanically, ZHX2 suppressed liver CSCs via inhibiting KDM2A-mediated demethylation of histone H3 lysine 36 (H3K36) at the promoter regions of stemness-associated transcription factors, such as NANOG, SOX4 and OCT4. Moreover, patients with lower expression of ZHX2 and higher expression of KDM2A in tumor tissues showed significantly poorer survival.
conclusionZHX2 counteracts stem cell traits through transcriptionally repressing KDM2A in HCC. Our data will aid in a better understanding of molecular mechanisms underlying HCC relapse and drug resistance.
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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.