The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death induced by tumor necrosis factor alpha in hepatocellular carcinoma

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• 作者：Xiao Xu ; Di Lu ; Runzhou Zhuang ; Xuyong Wei ; Haiyang Xie ; Chao Wang ; Yangbo Zhu ; Jianguo Wang ; Cheng Zhong ; Xuanyu Zhang ; Qiang Wei ; Zenglei He ; Lin Zhou and Shusen Zheng
• 刊名：Molecular Carcinogenesis
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：55
• 期：9
• 页码：1299-1308
• 全文大小：1654K
• ISSN：1098-2744

文摘

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 H₂O₂, 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.