Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells

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（e...

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Published in:Journal of Zhejiang University. B. Science 2013-06, Vol.14 (6), p.460-467
Main Authors: Xu, Guo-dong, Shi, Xin-bao, Sun, Le-bo, Zhou, Qing-yun, Zheng, Da-wei, Shi, Huo-shun, Che, Yong-liang, Wang, Zi-shan, Shao, Guo-feng
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - physiopathology
Cell Line, Tumor
Cell Movement - genetics
Cell Survival - genetics
Down-Regulation - genetics
Epithelial-Mesenchymal Transition - genetics
Eukaryotic Translation Initiation Factor 5A
Gene Knockdown Techniques - methods
Humans
Lung cancer
Peptide Initiation Factors - genetics
RNA-Binding Proteins - genetics
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Summary: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.
ISSN:1673-1581
1862-1783
DOI:10.1631/jzus.B1200200