ArticleCell death and differentiation2020
Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 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
- Prognostic Relevance of Neddylation-Related Genes in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Association of high-density lipoprotein with P1NP and β-CTX in hospitalized patients with osteoporotic fractures: a retrospective cross-sectional study.Frontiers in endocrinology · 2026Article
- 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
- The impact of metabolic reprogramming in hepatocellular carcinoma on T cell.Frontiers in immunology · 2025Review
- Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer.Cancer communications (London, England) · 2024Article
- The significance of lipid metabolism reprogramming of tumor-associated macrophages in hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2024Review
- Review
- Triptolide Reduces Neoplastic Progression in Hepatocellular Carcinoma by Downregulating the Lipid Lipase Signaling Pathway.Cancers · 2024Article
- Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.International journal of biological sciences · 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
- The Effects of a Low Linoleic Acid/α-Linolenic Acid Ratio on Lipid Metabolism and Endogenous Fatty Acid Distribution in Obese Mice.International journal of molecular sciences · 2023Article
- Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer.Applied microbiology and biotechnology · 2023Article
- The functions and roles of C2H2 zinc finger proteins in hepatocellular carcinoma.Frontiers in physiology · 2023Review
- The Emerging Role of Tumor Microenvironmental Stimuli in Regulating Metabolic Rewiring of Liver Cancer Stem Cells.Cancers · 2022Review
- 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
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD-HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD-HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
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