title: Silencing PRDX3 Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells.
abstract: PRDX3 is a mitochondrial peroxide reductase that regulates cellular redox state. It has been reported that PRDX3 is overexpressed in liver cancer, but how PRDX3 is involved in hepatocellular carcinoma (HCC) tumorigenesis and progression has not been well-characterized. In the present study, we established two stable cell lines by overexpressing or knocking down PRDX3 in HepG2 cells. We found that PRDX3 silencing decreased the growth rate of HepG2 cells and increased mtDNA oxidation. Quantitative proteomics identified 475 differentially expressed proteins between the PRDX3 knockdown and the control cells. These proteins were involved in antioxidant activity, angiogenesis, cell adhesion, cell growth, ATP synthesis, nucleic acid binding, redox, and chaperones. PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation. Taken together, our results indicate that PRDX3 promotes HCC growth and mediates cell migration and invasiveness and is a potential therapeutic target for HCC treatment.
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University , Beijing, 100084 China.
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University , Beijing, 100084 China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University , Beijing, 100084 China.
authors.forename: Haisha
authors.initials: H
authors.lastname: Liang
authors.affiliation: Center of Biomedical Analysis, Tsinghua University , Beijing, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Sun
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University , Beijing, 100084 China.
authors.forename: Shan
authors.initials: S
authors.lastname: Feng
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University , Beijing, 100084 China.|Center of Biomedical Analysis, Tsinghua University , Beijing, China.
authors.forename: Haiteng
authors.initials: H
authors.lastname: Deng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D061105:Peroxiredoxin III / Q000235:genetics / Q000494:pharmacology*
chemical_list: C516115:PRDX3 protein, human; D061105:Peroxiredoxin III
keywords: ATP synthase; PRDX3; TIMP1; cell growth; invasion; proteomics