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http://purl.uniprot.org/citations/25065598http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25065598http://www.w3.org/2000/01/rdf-schema#comment"Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. Gα12 gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report Gα12 overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. Gα12 expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of Gα12 (Gα12QL) deregulated microRNA (miRNA or miR)-200b/a/429, -194-2/192 and -194-1/215 clusters in the miRNome. cDNA microarray analyses disclosed the targets affected by Gα12 gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by Gα12. Decreases of miR-200a/b, -192 and -215 by Gα12 caused ZEB1 induction. The ability of Gα12 to decrease p53 levels, as a result of activating protein-1 (AP-1)/c-Jun-mediated mouse double minute 2 homolog induction, contributed to transcriptional deregulation of the miRNAs. Gα12QL induced ZEB1 and other epithelial-mesenchymal transition markers with fibroblastoid phenotype change. Consistently, transfection with miR-200b, -192 or -215 mimic prevented the ability of Gα12QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of Gα12 decreased the overall growth rate and average volume of tumors derived from SK-Hep1 cell (mesenchymal-typed). In HCC patients, miR-192, -215 and/or -200a were deregulated with microvascular invasion or growth advantage. In the HCC samples with higher Gα12 level, a correlation existed in the comparison of relative changes of Gα12 and ZEB1. In conclusion, Gα12 overexpressed in HCC causes ZEB1 induction by deregulating p53-responsive miRNAs, which may facilitate epithelial-mesenchymal transition and growth of liver tumor. These findings highlight the significance of Gα12 upregulation in liver tumor progression, implicating Gα12 as an attractive therapeutic target."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.org/dc/terms/identifier"doi:10.1038/onc.2014.218"xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"An J."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Kim S.H."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Lee S.J."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Lee W.H."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Lee S.K."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Kim E.S."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Lee C.H."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Park J.W."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Moon A."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Kim S.G."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Hwang S."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Lee C.G."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Kim K.M."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Yang Y.M."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/author"Dhanasekaran D.N."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/name"Oncogene"xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/pages"2910-2921"xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/title"Galpha12 gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma."xsd:string
http://purl.uniprot.org/citations/25065598http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/25065598http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25065598
http://purl.uniprot.org/citations/25065598http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25065598
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