Oncotarget

Research Papers:

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

Mi-Young Cho, Jae Youn Cheong, Wonchung Lim, Sujin Jo, Youngsoo Lee, Hee-Jung Wang, Kyou-Hoon Han and Hyeseong Cho _

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Oncotarget. 2014; 5:12233-12246. https://doi.org/10.18632/oncotarget.2625

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Abstract

Mi-Young Cho1,2, Jae Youn Cheong3, Wonchung Lim1,7, Sujin Jo4, Youngsoo Lee4, Hee-Jung Wang5, Kyou-Hoon Han6 and Hyeseong Cho1,2,4

1 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, The Graduate School, Ajou University, Suwon, Korea

2 Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, Korea

3 Department of Gastroenterology, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea

4 Genomic Instability Research Center, Ajou University School of Medicine, Suwon, Korea

5 Department of Surgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea

6 Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

7 Current address: Department of Sports Medicine, Cheongju University, Cheongju, Korea

Correspondence:

Hyeseong Cho, email:

Keywords: HBx, Liver cancer, Catalase, Cysteine, ROS

Received: July 23, 2014 Accepted: October 23, 2014 Published: October 24, 2014

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.


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