1. Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells.
- Author
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Xi, Hao, Gao, Yao-Hui, Han, Dong-Yan, Li, Qian-Yu, Feng, Li-Jin, Zhang, Wei, Ji, Guo, Xiao, Jia-Cheng, Zhang, Hui-Zhen, and Wei, Qing
- Subjects
HYPOXIA-inducible factor 1 ,PEROXIREDOXINS ,PROTEIN expression ,CELL proliferation ,THIOREDOXIN ,ANTIOXIDANTS - 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 (H 2 O 2 ). 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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