Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells

FEBS Lett. 2014 Sep 17;588(18):3390-4. doi: 10.1016/j.febslet.2014.07.030. Epub 2014 Aug 2.

Abstract

Peroxiredoxin 3 (Prx3) is a mitochondrial member of the antioxidant family of thioredoxin peroxidases that uses mitochondrial thioredoxin 2 as a source of reducing equivalents to scavenge hydrogen peroxide (H2O2). Here, we report that the protein levels of Prx3 are significantly reduced in VHL-deficient clear cell renal cell carcinoma (CCRCC). Furthermore, stabilization of HIF-1α protein, caused either by VHL deficiency under normoxia, or by hypoxia, significantly reduced Prx3 expression. Luciferase-reporter and chromatin-immunoprecipitation assays indicated that HIF-1α binds to the hypoxia-responsive elements of PRDX3 promoter and represses its transcription. Finally, shRNA-based assays suggested that Prx3 downregulation is required for the HIF-1α-dependent proliferation of CCRCC cells. Taken together, our results shed new light onto the mechanism of HIF-1α-dependent proliferation in CCRCC cells.

Keywords: HIF-1α; Proliferation; Prx3; VHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / enzymology*
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Proliferation*
  • Enzyme Repression
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • Kidney Neoplasms / enzymology*
  • Peroxiredoxin III / genetics
  • Peroxiredoxin III / metabolism*
  • Response Elements
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • PRDX3 protein, human
  • Peroxiredoxin III
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human