Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 이창호 | - |
dc.date.accessioned | 2016-11-17T02:29:29Z | - |
dc.date.available | 2016-11-17T02:29:29Z | - |
dc.date.issued | 2015-05 | - |
dc.identifier.citation | ONCOGENE, v. 34, NO 22, Page. 2910-2921 | en_US |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.issn | 1476-5594 | - |
dc.identifier.uri | http://www.nature.com/onc/journal/v34/n22/full/onc2014218a.html | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11754/24420 | - |
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. | en_US |
dc.description.sponsorship | This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2007-0056817) and in part by the World Class University project (R322012000100980) and National Cancer Center (No. 1110050). We thank Prof Dr Soon-Sun Hong and Hee-Seung Lee for their indispensable support. | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.subject | HETEROTRIMERIC G-PROTEINS | en_US |
dc.subject | KAPPA-B-ALPHA | en_US |
dc.subject | SPHINGOSINE 1-PHOSPHATE | en_US |
dc.subject | P53-INDUCIBLE MICRORNAS | en_US |
dc.subject | ACTIN CYTOSKELETON | en_US |
dc.subject | CANCER INVASION | en_US |
dc.subject | DOWN-REGULATION | en_US |
dc.subject | TARGETING ZEB1 | en_US |
dc.subject | MIR-200 FAMILY | en_US |
dc.subject | TUMOR-GROWTH | en_US |
dc.title | G alpha(12) gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma | en_US |
dc.type | Article | en_US |
dc.relation.no | 22 | - |
dc.relation.volume | 34 | - |
dc.identifier.doi | 10.1038/onc.2014.218 | - |
dc.relation.page | 2910-2921 | - |
dc.relation.journal | ONCOGENE | - |
dc.contributor.googleauthor | Yang, Y. M. | - |
dc.contributor.googleauthor | Lee, W. H. | - |
dc.contributor.googleauthor | Lee, C. G. | - |
dc.contributor.googleauthor | An, J. | - |
dc.contributor.googleauthor | Kim, E-S | - |
dc.contributor.googleauthor | Kim, S. H. | - |
dc.contributor.googleauthor | Lee, S-K | - |
dc.contributor.googleauthor | Lee, C. H. | - |
dc.contributor.googleauthor | Dhanasekaran, D. N. | - |
dc.contributor.googleauthor | Moon, A. | - |
dc.relation.code | 2015000098 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | jennysue | - |
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