ArticleGastroenterology2012
Zinc fingers and homeoboxes 2 inhibits hepatocellular carcinoma cell proliferation and represses expression of Cyclins A and E.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 101 citations in OpenAlex.
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Data-Driven Discovery of a Key Regulator Cyclin A2 as a Promising Therapeutic Target in Hormone-Sensitive Cancers.Molecular biotechnology · 2026Article
- In Silico Assessment ofJournal of pharmacopuncture · 2025Article
- Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2.Leukemia · 2025Article
- ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2.Nutrition & diabetes · 2025Article
- Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma.Nature reviews. Urology · 2024Review
- Construction and validation of a chromatin regulator-related gene signature for prognostic and therapeutic significance of clear cell renal cell carcinoma.Translational cancer research · 2024Article
- Relationship between ZHX2 Expression and VHL Gene Alteration in VHL-associated and Sporadic Hemangioblastomas of the Central Nervous System.Journal of kidney cancer and VHL · 2024Article
- Elongation of very long chain fatty acids-3 (American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 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
- ZHX2 deficiency enriches hybrid MET cells through regulating E-cadherin expression.Cell death & disease · 2023Article
- Decreased zinc-fingers and homeoboxes family expression was associated with unfavorable outcomes and immune infiltration in lung adenocarcinoma.Translational cancer research · 2023Article
- Article
- Zinc fingers and homeoboxes 2 is required for diethylnitrosamine-induced liver tumor formation in C57BL/6 mice.Hepatology communications · 2022Article
- Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword.International journal of molecular sciences · 2022Review
- USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Attenuated ZHX3 expression is predictive of poor outcome for liver cancer: Indication for personalized therapy.Oncology letters · 2022Article
- LINC01431 Promotes Histone H4R3 Methylation to Impede HBV Covalently Closed Circular DNA Transcription by Stabilizing PRMT1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsZinc-fingers and homeoboxes 2 (ZHX2) represses transcription of several genes associated with liver cancer. However, little is known about the role of ZHX2 in the development of hepatocellular carcinoma (HCC). We investigated the mechanisms by which ZHX2 might affect proliferation of HCC cells.
methodsWe overexpressed and knocked down ZHX2 in HCC cells and analyzed the effects on proliferation, colony formation, and the cell cycle. We also analyzed the effects of ZHX2 overexpression in growth of HepG2.2.15 tumor xenografts in nude mice. Chromatin immunoprecipitation and luciferase reporter assays were used to measure binding of ZHX2 target promoters. Levels of ZHX2 in HCC samples were evaluated by immunohistochemistry.
resultsZHX2 overexpression significantly reduced proliferation of HCC cells and growth of tumor xenografts in mice; it led to G1 arrest and reduced levels of Cyclins A and E in HCC cell lines. ZHX2 bound to promoter regions of CCNA2 (which encodes Cyclin A) and CCNE1 (which encodes Cyclin E) and inhibited their transcription. Knockdown of Cyclin A or Cyclin E reduced the increased proliferation mediated by ZHX2 knockdown. Nuclear localization of ZHX2 was required for it to inhibit proliferation of HCC cells in culture and in mice. Nuclear localization of ZHX2 was reduced in human HCC samples, even in small tumors (diameter, <5 cm), compared with adjacent nontumor tissues. Moreover, reduced nuclear levels of ZHX2 correlated with reduced survival times of patients, high levels of tumor microvascularization, and hepatocyte proliferation.
conclusionsZHX2 inhibits HCC cell proliferation by preventing expression of Cyclins A and E, and reduces growth of xenograft tumors in mice. Loss of nuclear ZHX2 might be an early step in the development of HCC.
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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.