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Hypoxia inducible factor‐1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells
Author(s) -
Xi Hao,
Gao Yao-Hui,
Han Dong-Yan,
Li Qian-Yu,
Feng Li-Jin,
Zhang Wei,
Ji Guo,
Xiao Jia-Cheng,
Zhang Hui-Zhen,
Wei Qing
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.07.030
Subject(s) - peroxiredoxin , chromatin immunoprecipitation , clear cell renal cell carcinoma , small hairpin rna , hypoxia inducible factors , downregulation and upregulation , thioredoxin , transcription factor , cell growth , microbiology and biotechnology , immunoprecipitation , chemistry , biology , apoptosis , cancer research , peroxidase , biochemistry , oxidative stress , gene expression , promoter , enzyme , medicine , gene , renal cell carcinoma , gene knockdown
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.