G alpha(12) gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma
DC Field | Value | Language |
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dc.contributor.author | Yang, Y. M. | - |
dc.contributor.author | Lee, W. H. | - |
dc.contributor.author | Lee, C. G. | - |
dc.contributor.author | An, J. | - |
dc.contributor.author | Kim, E-S | - |
dc.contributor.author | Kim, S. H. | - |
dc.contributor.author | Lee, S-K | - |
dc.contributor.author | Lee, C. H. | - |
dc.contributor.author | Dhanasekaran, D. N. | - |
dc.contributor.author | Moon, A. | - |
dc.contributor.author | Hwang, S. | - |
dc.contributor.author | Lee, S. J. | - |
dc.contributor.author | Park, J-W | - |
dc.contributor.author | Kim, K. M. | - |
dc.contributor.author | Kim, S. G. | - |
dc.date.available | 2020-02-28T09:42:56Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-05-28 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10510 | - |
dc.description.abstract | Hepatocellular carcinoma (HCC) has a poor prognosis owing to aggressive phenotype. G alpha(12) gep oncogene product couples to G-protein-coupled receptors, whose ligand levels are frequently increased in tumor microenvironments. Here, we report G alpha(12) overexpression in human HCC and the resultant induction of zinc-finger E-box-binding homeobox 1 (ZEB1) as mediated by microRNA deregulation. G alpha(12) expression was higher in HCC than surrounding non-tumorous tissue. Transfection of Huh7 cell with an activated mutant of G alpha(12) (G alpha(12)QL) 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 G alpha(12) gene knockout. An integrative network of miRNAs and mRNA changes enabled us to predict ZEB1 as a key molecule governed by G alpha(12). Decreases of miR-200a/b, -192 and -215 by G alpha(12) caused ZEB1 induction. The ability of G alpha(12) 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. G alpha(12)QL 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 G alpha(12)QL to increase tumor cell migration/invasion. In xenograft studies, sustained knockdown of G alpha(12) 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 G alpha(12) level, a correlation existed in the comparison of relative changes of G alpha(12) and ZEB1. In conclusion, G alpha(12) 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 G alpha(12) upregulation in liver tumor progression, implicating G alpha(12) as an attractive therapeutic target. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | ONCOGENE | - |
dc.subject | HETEROTRIMERIC G-PROTEINS | - |
dc.subject | KAPPA-B-ALPHA | - |
dc.subject | SPHINGOSINE 1-PHOSPHATE | - |
dc.subject | P53-INDUCIBLE MICRORNAS | - |
dc.subject | ACTIN CYTOSKELETON | - |
dc.subject | CANCER INVASION | - |
dc.subject | DOWN-REGULATION | - |
dc.subject | TARGETING ZEB1 | - |
dc.subject | MIR-200 FAMILY | - |
dc.subject | TUMOR-GROWTH | - |
dc.title | G alpha(12) gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000355324300010 | - |
dc.identifier.doi | 10.1038/onc.2014.218 | - |
dc.identifier.bibliographicCitation | ONCOGENE, v.34, no.22, pp.2910 - 2921 | - |
dc.identifier.scopusid | 2-s2.0-84930084059 | - |
dc.citation.endPage | 2921 | - |
dc.citation.startPage | 2910 | - |
dc.citation.title | ONCOGENE | - |
dc.citation.volume | 34 | - |
dc.citation.number | 22 | - |
dc.contributor.affiliatedAuthor | Lee, S. J. | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | HETEROTRIMERIC G-PROTEINS | - |
dc.subject.keywordPlus | KAPPA-B-ALPHA | - |
dc.subject.keywordPlus | SPHINGOSINE 1-PHOSPHATE | - |
dc.subject.keywordPlus | P53-INDUCIBLE MICRORNAS | - |
dc.subject.keywordPlus | ACTIN CYTOSKELETON | - |
dc.subject.keywordPlus | CANCER INVASION | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | TARGETING ZEB1 | - |
dc.subject.keywordPlus | MIR-200 FAMILY | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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