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Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.

Authors
Cho, MY; Cheong, JY; Lim, W; Jo, S; Lee, Y; Wang, HJ; Han, KH; Cho, H
Citation
Oncotarget, 5(23):12233-12246, 2014
Journal Title
Oncotarget
ISSN
1949-2553
Abstract
Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys-) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys- cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases.
MeSH terms
Blotting, WesternCarcinoma, Hepatocellular/enzymologyCarcinoma, Hepatocellular/virologyCatalase/metabolismCell Proliferation/physiologyCysteineFemaleHepatitis B/complicationsHumansLiver Neoplasms/enzymologyLiver Neoplasms/virologyMaleOxidative StressPrognosisProtein StabilityReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionTrans-Activators/chemistryTrans-Activators/metabolism
DOI
10.18632/oncotarget.2625
PMID
25361011
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
Journal Papers > Research Organization > Genomic Instability Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
정, 재연이, 영수왕, 희정조, 혜성
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