title: Hypoxia inducible factor-1α suppresses Peroxiredoxin 3 expression to promote proliferation of CCRCC cells.
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.
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xi
authors.affiliation: Department of Science and Education, Minghang Central Hospital, Shanghai 201100, PR China.
authors.forename: Yao-Hui
authors.initials: YH
authors.lastname: Gao
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Han
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Qian-Yu
authors.initials: QY
authors.lastname: Li
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Feng
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Guo
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China.
authors.forename: Jia-Cheng
authors.initials: JC
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, PR China. Electronic address: zhanghuizhen1967@sina.com.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, PR China. Electronic address: weiqing1971@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
mesh_terms: D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004794:Enzyme Repression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D007680:Kidney Neoplasms / Q000201:enzymology*; D061105:Peroxiredoxin III / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: HIF-1α; Proliferation; Prx3; VHL