title: Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, The Graduate School, Ajou University, Suwon, Korea. Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, The Graduate School, Ajou University, Suwon, Korea. Current address: Department of Sports Medicine, Cheongju University, Cheongju, Korea.
authors.forename: Wonchung
authors.initials: W
authors.lastname: Lim
authors.affiliation: Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Jo
authors.affiliation: Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Surgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Kyou-Hoon
authors.initials: KH
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, The Graduate School, Ajou University, Suwon, Korea. Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, Korea. Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000821:virology*; D002374:Catalase / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D003545:Cysteine; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000821:virology*; D008297:Male; D018384:Oxidative Stress; D011379:Prognosis; D055550:Protein Stability; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D017382:Reactive Oxygen Species; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D002374:Catalase; D003545:Cysteine