Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G611-22. doi: 10.1152/ajpgi.00160.2014. Epub 2014 Jul 3.

Abstract

Hepatocellular carcinoma (HCC) is regarded as a major global health care issue, and chronic hepatitis B virus (HBV) infection is considered to be involved in pathogenesis of HCC. To increase knowledge of HCC pathogenesis, as well as discover potential novel molecules for anti-cancer therapy, mass spectrometry and isobaric tag for relative and absolute quantitation (iTARQ) were employed. The differences between nine HBV-related HCC and adjacent non-HCC tissue specimens were studied. In total, 222 proteins were analyzed for differential expression in the two types of samples. Among these proteins, several were further confirmed by immunohistochemical, immunoblotting, and real-time RT-PCR analysis. RNA interference induced downregulation of glucose-6-phosphate dehydrogenase (G6PD) and decreased HBV replication by fivefold by the IFN pathway. Decreased G6PD expression resulted in decreased hepatoma cell migration and invasion in cell culture. In summary, the investigation provides new information on pathogenesis of HBV infection and suggests G6PD as a novel anti-HCC target. G6PD suppression may contribute to treatment strategies for inhibiting tumor progression.

Keywords: G6PD; HBV; HCC; iTRAQ; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Cell Movement
  • Chromatography, Liquid
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glucosephosphate Dehydrogenase / genetics
  • Glucosephosphate Dehydrogenase / metabolism*
  • Hep G2 Cells
  • Hepatitis B / complications*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development
  • Hepatitis B virus / metabolism*
  • Humans
  • Immunohistochemistry
  • Interferon Type I / metabolism
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Proteomics / methods
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tandem Mass Spectrometry
  • Tissue Array Analysis
  • Transfection
  • Virus Replication

Substances

  • Biomarkers, Tumor
  • Interferon Type I
  • Glucosephosphate Dehydrogenase