Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0085318
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dc.titleOverexpression of endothelin 1 triggers hepatocarcinogenesis in zebrafish and promotes cell proliferation and migration through the AKT pathway
dc.contributor.authorLu J.-W.
dc.contributor.authorLiao C.-Y.
dc.contributor.authorYang W.-Y.
dc.contributor.authorLin Y.-M.
dc.contributor.authorJin S.-L.C.
dc.contributor.authorWang H.-D.
dc.contributor.authorYuh C.-H.
dc.date.accessioned2019-11-05T02:05:10Z
dc.date.available2019-11-05T02:05:10Z
dc.date.issued2014
dc.identifier.citationLu 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
dc.identifier.issn1932-6203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161437
dc.description.abstractHepatocarcinogenesis 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.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectactivating transcription factor 6
dc.subjectendothelin 1
dc.subjectfluorescent dye
dc.subjectglycogen
dc.subjectmCherry
dc.subjectmicroRNA 1
dc.subjectprotein IRE1
dc.subjectprotein kinase
dc.subjectprotein kinase B
dc.subjectprotein PERK
dc.subjectRNA
dc.subjectunclassified drug
dc.subjectX box binding protein 1
dc.subjectadult
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectbile duct dilatation
dc.subjectcancer growth
dc.subjectcancer patient
dc.subjectcell culture
dc.subjectcell migration
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectembryo
dc.subjectfatty liver
dc.subjectgene expression regulation
dc.subjectglycogen metabolism
dc.subjectin vitro study
dc.subjectliver cancer
dc.subjectliver carcinogenesis
dc.subjectliver fibrosis
dc.subjectliver hyperplasia
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectprotein analysis
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectRNA splicing
dc.subjectsignal transduction
dc.subjecttissue specificity
dc.subjecttransgenic animal
dc.subjectunfolded protein response
dc.subjectupregulation
dc.subjectxenotransplantation
dc.subjectzebra fish
dc.subjectAnimals
dc.subjectCarcinoma, Hepatocellular
dc.subjectCell Cycle
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectEndothelin-1
dc.subjectFatty Liver
dc.subjectGene Expression
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectLiver Cirrhosis
dc.subjectLiver Neoplasms
dc.subjectMicroRNAs
dc.subjectPhosphatidylinositol 3-Kinases
dc.subjectProtein Kinase Inhibitors
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectUnfolded Protein Response
dc.subjectZebrafish
dc.subjectZebrafish Proteins
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1371/journal.pone.0085318
dc.description.sourcetitlePLoS ONE
dc.description.volume9
dc.description.issue1
dc.description.pagee85318
dc.published.statePublished
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