Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 고광석 | * |
dc.date.accessioned | 2016-12-28T02:12:35Z | - |
dc.date.available | 2016-12-28T02:12:35Z | - |
dc.date.issued | 2016 | * |
dc.identifier.issn | 0021-9258 | * |
dc.identifier.other | OAK-19725 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/233336 | - |
dc.description.abstract | Prohibitin 1 (PHB1) is a mitochondrial chaperone that regulates cell growth. Phb1 knock-out mice exhibit liver injury and hepatocellular carcinoma (HCC). Phb1 knock-out livers show induction of tumor growth-associated genes, H19 and insulin-like growth factor 2 (Igf2). These genes are controlled by the imprinting control region (ICR) containing CCCTC-binding transcription factor (CTCF)-binding sites. Because Phb1 knock-out mice exhibited induction of H19 and Igf2, we hypothesized that PHB1-mediated regulation of the H19-Igf2 axis might control cell proliferation in normal hepatocytes. H19 and Igf2 were induced (8-20-fold) in 3-week-old Phb1 knock-out livers, in Phb1 siRNA-treated AML12 hepatocytes (2-fold), and HCC cell lines when compared with control. Phb1 knockdown lowered CTCF protein in AML12 by ∼30% when compared with control. CTCF overexpression lowered basal H19 and Igf2 expression by 30% and suppressed Phb1 knockdown-mediated induction of these genes. CTCF and PHB1 co-immunoprecipitated and colocalized on the ICR element, and Phb1 knockdown lowered CTCF ICR binding activity. The results suggest that PHB1 and CTCF cooperation may control the H19-Igf2 axis. Human HCC tissues with high levels of H19 and IGF2 exhibited a 40-50% reduction in PHB1 and CTCF expression and their ICR binding activity. Silencing Phb1 or overexpressing H19 in the mouse HCC cell line, SAMe-D, induced cell growth. Blocking H19 induction prevented Phb1 knockdown-mediated growth, whereas H19 overexpression had the reverse effect. Interestingly H19 silencing induced PHB1 expression. Taken together, our results demonstrate that the H19-Igf2 axis is negatively regulated by CTCF-PHB1 cooperation and that H19 is involved in modulating the growth-suppressive effect of PHB1 in the liver. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. | * |
dc.language | English | * |
dc.publisher | American Society for Biochemistry and Molecular Biology Inc. | * |
dc.title | Prohibitin 1 regulates the H19-Igf2 axis and proliferation in hepatocytes | * |
dc.type | Article | * |
dc.relation.issue | 46 | * |
dc.relation.volume | 291 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 24148 | * |
dc.relation.lastpage | 24159 | * |
dc.relation.journaltitle | Journal of Biological Chemistry | * |
dc.identifier.doi | 10.1074/jbc.M116.744045 | * |
dc.identifier.wosid | WOS:000388498100030 | * |
dc.identifier.scopusid | 2-s2.0-84994527593 | * |
dc.author.google | Ramani K. | * |
dc.author.google | Mavila N. | * |
dc.author.google | Ko K.S. | * |
dc.author.google | Mato J.M. | * |
dc.author.google | Lu S.C. | * |
dc.contributor.scopusid | 고광석(25027852000) | * |
dc.date.modifydate | 20240301081003 | * |