ArticlePloS one2014
Overexpression of endothelin 1 triggers hepatocarcinogenesis in zebrafish and promotes cell proliferation and migration through the AKT pathway.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 75 citations in OpenAlex.
- Assessment of peripheral gene expression signatures as predictive biomarkers for hepatocellular carcinoma following DAA treatment.Journal, genetic engineering & biotechnology · 2025Article
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- Insulin-mediated endothelin signaling is antiviral during West Nile virus infection.bioRxiv : the preprint server for biology · 2023Article
- Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- κB signaling pathways.Clinical and molecular hepatology · 2022Article
- Article
- Systems analysis identifies endothelin 1 axis blockade for enhancing the anti-tumor effect of multikinase inhibitor.Cancer gene therapy · 2022Article
- Review
- The Persistence of Hepatitis C Virus Infection in Hepatocytes Promotes Hepatocellular Carcinoma Progression by Pro-Inflammatory Interluekin-8 Expression.Biomedicines · 2021Article
- C5a Activates a Pro-Inflammatory Gene Expression Profile in Human Gaucher iPSC-Derived Macrophages.International journal of molecular sciences · 2021Article
- Lipopolysaccharides Enhance Epithelial Hyperplasia and Tubular Adenoma in Intestine-Specific Expression ofBiomedicines · 2021Article
- The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation.Frontiers in immunology · 2021Review
- Loss of TARBP2 Drives the Progression of Hepatocellular CarcinomaFrontiers in oncology · 2021Article
- Low molecular weight fucoidan inhibits hepatocarcinogenesis and nonalcoholic fatty liver disease in zebrafish via ASGR/STAT3/HNF4A signaling.Clinical and translational medicine · 2020Article
- Review
- Genetic Engineering of Zebrafish in Cancer Research.Cancers · 2020Review
- Anticancer effect of caudatin in diethylnitrosamine‑induced hepatocarcinogenesis in rats.Molecular medicine reports · 2020Article
- Review
- Low Molecular Weight Fucoidan Prevents Radiation-Induced Fibrosis and Secondary Tumors in a Zebrafish Model.Cancers · 2020Article
- Transcriptomically Revealed Oligo-Fucoidan Enhances the Immune System and Protects Hepatocytes via the ASGPR/STAT3/HNF4A Axis.Biomolecules · 2020Article
- Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocarcinogenesis commonly involves the gradual progression from hepatitis to fibrosis and cirrhosis, and ultimately to hepatocellular carcinoma (HCC). Endothelin 1 (Edn1) has been identified as a gene that is significantly up-regulated in HBx-induced HCC in mice. In this study, we further investigated the role of edn1 in hepatocarcinogenesis using a transgenic zebrafish model and a cell culture system. Liver-specific edn1 expression caused steatosis, fibrosis, glycogen accumulation, bile duct dilation, hyperplasia, and HCC in zebrafish. Overexpression of EDN1 in 293T cells enhanced cell proliferation and cell migration in in vitro and xenotransplantation assays and was accompanied with up-regulation of several cell cycle/proliferation- and migration-specific genes. Furthermore, expression of the unfolded protein response (UPR) pathway-related mediators, such as spliced XBP1, ATF6, IRE1, and PERK, was also up-regulated at both the RNA and protein levels. In the presence of an EDN1 inhibitor or an AKT inhibitor, these increases were diminished and the EDN1-induced migration ability also was disappeared, suggesting that the EDN1 effects act through activation of the AKT pathway to enhance the UPR and subsequently activate the expression of downstream genes. Additionally, p-AKT is enhanced in the edn1 transgenic fish compared to the GFP-mCherry control. The micro RNA miR-1 was found to inhibit the expression of EDN1. We also observed an inverse correlation between EDN1 and miR-1 expression in HCC patients. In conclusion, our data suggest that EDN1 plays an important role in HCC progression by activating the PI3K/AKT pathway and is regulated by miR-1.
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