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

Mol Carcinog. 2016 Sep;55(9):1299-308. doi: 10.1002/mc.22371. Epub 2015 Aug 21.

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.

Keywords: apoptosis; hepatectomy; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Liver / metabolism
  • Liver / pathology*
  • Liver Neoplasms / blood
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Peroxiredoxin VI / blood
  • Peroxiredoxin VI / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Tumor Necrosis Factor-alpha
  • Peroxiredoxin VI