title: The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death induced by tumor necrosis factor alpha in hepatocellular carcinoma.
abstract: In this study, we used proteomic profiling to compare hepatocellular carcinoma (HCC) and peri-tumoral tissues to identify potential tumor markers of HCC. We identified eight differentially expressed proteins (>3-fold), including Peroxiredoxin 6 (PRDX6). PRDX6 is a bifunctional enzyme with both peroxidase and calcium-independent phospholipase A2 (iPLA2) activity. We found that peri-tumoral tissues expressed higher levels of PRDX6 mRNA (n = 59, P = 0.018) and protein (n = 265, P < 0.001) than HCC tissues, and that decreased expression of PRDX6 in HCC tissues was an independent risk factor indicating a poor prognosis (n = 145, P = 0.007). Combining the examination of serum PRDX6 with α-fetoprotein improved the diagnostic sensitivity of tests for HCC compared to α-fetoprotein alone (85.0% vs 50.0%, n = 40). We found that PRDX6 induced S phase arrest in HCC cells and inhibited HCC tumorigenicity in mice injected with cancer cells. When treated with H2 O2 , PRDX6 inhibited apoptosis. When treated with tumor necrosis factor alpha (TNF-α), PRDX6 promoted apoptosis. Inhibition of iPLA2 activity of PRDX6 decreased the apoptosis induced by TNF-α. In conclusion, PRDX6 inhibited the carcinogenesis of HCC, and the iPLA2 activity of PRDX6 promoted cancer cell death induced by TNF-α. © 2015 Wiley Periodicals, Inc.
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Xiao
authors: X
authors: Xu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Di
authors: D
authors: Lu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Runzhou
authors: R
authors: Zhuang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Xuyong
authors: X
authors: Wei
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Haiyang
authors: H
authors: Xie
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Chao
authors: C
authors: Wang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Yangbo
authors: Y
authors: Zhu
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Jianguo
authors: J
authors: Wang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Cheng
authors: C
authors: Zhong
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Xuanyu
authors: X
authors: Zhang
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Qiang
authors: Q
authors: Wei
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Zenglei
authors: Z
authors: He
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Lin
authors: L
authors: Zhou
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.|Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors: Shusen
authors: S
authors: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D054465:Peroxiredoxin VI / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D054465:Peroxiredoxin VI
keywords: apoptosis; hepatectomy; proteomics