title: Decreased selenium-binding protein 1 enhances glutathione peroxidase 1 activity and downregulates HIF-1α to promote hepatocellular carcinoma invasiveness.
abstract: OBJECTIVE
  We aimed to characterize the role of selenium-binding protein 1 (SBP1) in hepatocellular carcinoma (HCC) invasiveness and underlying clinical significance.
  
  
  METHODS
  SBP1 expression was measured in stepwise metastatic HCC cell lines by Western blotting. The role of SBP1 in HCC was investigated using siRNA. Immunofluorescence analyses were used to detect the interaction between SBP1 and glutathione peroxidase 1 (GPX1). Nineteen fresh tumor tissues and 323 paraffin-embedded samples were used to validate in vitro findings and to detect the prognostic significance of SBP1, respectively.
  
  
  RESULTS
  Inhibition of SBP1 effectively increased cell motility, promoted cell proliferation, and inhibited apoptosis only under oxidative stress; it also greatly enhanced GPX1 activity without altering GPX1 expression and downregulated hypoxia-inducible factor-1α (HIF-1α) expression. SBP1 and GPX1 formed nuclear bodies and colocalized under oxidative stress. In freshly isolated clinical HCC tissues, decreased SBP1 was linked with increased GPX1 activity and correlated with vascular invasion. Tumor tissue microarrays indicated that SBP1 was an independent risk factor for overall survival and disease recurrence; patients with lower SBP1 expression experienced shorter overall survival periods and higher rates of disease recurrence (P < 0.001). Further analyses indicated that the predictive power of SBP1 was more significant for patients beyond the Milan criteria than patients within the Milan criteria.
  
  
  CONCLUSIONS
  Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1α expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC.
authors.affiliation: Liver Cancer Institute, Fudan University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Guangyu
authors.initials: G
authors.lastname: Ding
authors.forename: Chengyu
authors.initials: C
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Yifeng
authors.initials: Y
authors.lastname: He
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D011379:Prognosis; D051137:Selenium-Binding Proteins / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051137:Selenium-Binding Proteins; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human