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https://doi.org/10.1371/journal.pone.0085318
Title: | Overexpression of endothelin 1 triggers hepatocarcinogenesis in zebrafish and promotes cell proliferation and migration through the AKT pathway | Authors: | Lu J.-W. Liao C.-Y. Yang W.-Y. Lin Y.-M. Jin S.-L.C. Wang H.-D. Yuh C.-H. |
Keywords: | activating transcription factor 6 endothelin 1 fluorescent dye glycogen mCherry microRNA 1 protein IRE1 protein kinase protein kinase B protein PERK RNA unclassified drug X box binding protein 1 adult animal cell animal experiment animal model animal tissue article bile duct dilatation cancer growth cancer patient cell culture cell migration cell proliferation controlled study embryo fatty liver gene expression regulation glycogen metabolism in vitro study liver cancer liver carcinogenesis liver fibrosis liver hyperplasia nonhuman nucleotide sequence protein analysis protein expression protein function RNA splicing signal transduction tissue specificity transgenic animal unfolded protein response upregulation xenotransplantation zebra fish Animals Carcinoma, Hepatocellular Cell Cycle Cell Movement Cell Proliferation Endothelin-1 Fatty Liver Gene Expression HEK293 Cells Humans Liver Cirrhosis Liver Neoplasms MicroRNAs Phosphatidylinositol 3-Kinases Protein Kinase Inhibitors Proto-Oncogene Proteins c-akt Unfolded Protein Response Zebrafish Zebrafish Proteins |
Issue Date: | 2014 | Citation: | Lu J.-W., Liao C.-Y., Yang W.-Y., Lin Y.-M., Jin S.-L.C., Wang H.-D., Yuh C.-H. (2014). Overexpression of endothelin 1 triggers hepatocarcinogenesis in zebrafish and promotes cell proliferation and migration through the AKT pathway. PLoS ONE 9 (1) : e85318. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0085318 | Rights: | Attribution 4.0 International | 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) pathwayrelated 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. © 2014 Lu et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161437 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0085318 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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