Prohibitin-2 promotes hepatocellular carcinoma malignancy progression in hypoxia based on a label-free quantitative proteomics strategy

Mol Carcinog. 2014 Oct;53(10):820-32. doi: 10.1002/mc.22040. Epub 2013 May 9.

Abstract

The rapid growth of hepatocellular carcinoma (HCC) leading to tumor hypoxia is a common pathological phenomenon. Meanwhile, tumor hypoxia can promote a change in the biological properties of tumor cells. It may enhance the survival of tumor cells under stress conditions, resulting in resistance to apoptosis and angiogenesis. The moleculars that could modulate the malignant phenotypes of HCC cells remain largely unknown. Based on label-free quantitative proteomic data, we found a significant upregulation of prohibitin-2 (PHB2) in HCC tissues. Treatment of hepatoma cells with small interfering RNAs against PHB2 suppressed cell growth and colony formation, led to G1 phase arrest and sensitized HCC cells to apoptosis. Moreover, inhibition of PHB2 expression dramatically repressed the ability of HCC cells to adapt to hypoxic microenvironments and resist chemotherapy-induced apoptosis. Thus, PHB2 in HCC supports the development and progression of hepatocellular malignancy to hypoxia, and implicates the potential antagonist function of PHB2 in transarterial chemoembolization treatment.

Keywords: biomarker; hepatocellular carcinoma; label-free; prohibitin-2; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis
  • Carcinogenesis / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Hypoxia
  • Cell Movement
  • Cell Proliferation
  • G1 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Molecular Sequence Data
  • Prohibitins
  • Proteome / metabolism*
  • Proteomics
  • Repressor Proteins / physiology*
  • Transcriptome

Substances

  • PHB2 protein, human
  • Prohibitins
  • Proteome
  • Repressor Proteins