title: Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) is believed to be the critical process in malignant tumor invasion and metastases, and has a great influence on improving the survival rate in non-small-cell lung cancer (NSCLC) patients. Recent studies suggested that eukaryotic initiation factor 5A-2 (eIF5A-2) might serve as an adverse prognostic marker of survival. We detected eIF5A-2 in NSCLC A549 cells, and found that the invasive capability correlates with the eIF5A-2 expression.
  
  
  METHODS
  Transforming growth factor (TGF)-β1 was used to induce EMT in A549 cells. Western blotting, immunofluorescence, wound healing assay, and transwell-matrigel invasion chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of eIF5A-2. We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence. We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.
  
  
  RESULTS
  After stimulating with TGF-β1, almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities. These cells also had higher eIF5A-2 protein expression. Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.
  
  
  CONCLUSIONS
  The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. Furthermore, in the A549 cell line, the process of EMT phenotype change could be reversed by eIF5A-2 siRNA, with a consequent weakening of both invasive and metastatic capabilities.
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Lihuili Hospital, Ningbo Medical Center, Affiliated Hospital of Medical School, Ningbo University, Ningbo 315041, China.
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Xu
authors.forename: Xin-bao
authors.initials: XB
authors.lastname: Shi
authors.forename: Le-bo
authors.initials: LB
authors.lastname: Sun
authors.forename: Qing-yun
authors.initials: QY
authors.lastname: Zhou
authors.forename: Da-wei
authors.initials: DW
authors.lastname: Zheng
authors.forename: Huo-shun
authors.initials: HS
authors.lastname: Shi
authors.forename: Yong-liang
authors.initials: YL
authors.lastname: Che
authors.forename: Zi-shan
authors.initials: ZS
authors.lastname: Wang
authors.forename: Guo-feng
authors.initials: GF
authors.lastname: Shao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D055785:Gene Knockdown Techniques / Q000379:methods*; D006801:Humans; D010448:Peptide Initiation Factors / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A