Down-regulation of eIF5A-2 prevents epithelial-mesenchymal transition in non-small-cell lung cancer cells
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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.
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.
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.
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.
Key wordsNon-small-cell lung cancer (NSCLC) Epithelial-mesenchymal transition (EMT) Eukaryotic initiation factor 5A-2 (eIF5A-2) Transforming growth factor (TGF)-β1 A549
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- Chen, W., Luo, J.H., Hua, W.F., Zhou, F.J., Lin, M.C., Kung, H.F., Xie, D., 2009. Overexpression of EIF-5A2 is an independent predictor of outcome in patients of urothelial carcinoma of the bladder treated with radical cystectomy. Cancer Epidemiol. Biomarkers Prev., 18(2):400–408. [doi:10.1158/1055-9965.EPI-08-0754]PubMedCrossRefGoogle Scholar
- Nozawa, N., Hashimoto, S., Nakashima, Y., Matsuo, Y., Koga, T., Sugio, K., Sueishi, K., 2006. Immunohistochemical α- and β-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma. Pathol. Res. Pract., 202(9):639–650. [doi:10.1016/j. prp.2006.03.007]PubMedCrossRefGoogle Scholar
- Rosell, R., Felip, E., Taron, M., Majo, J., Mendez, P., Sanchez-Ronco, M., Maestre, J., 2004. Gene expression as a predictive marker of outcome in stage IIB-IIIA-IIIB non-small cell lung cancer after induction gemcitabine-based chemotherapy followed by resectional surgery. Clin. Cancer Res., 10(12):4215s–4219s. [doi:10.1158/1078-0432.CCR-040006]PubMedCrossRefGoogle Scholar
- Saito, R.A., Watabe, T., Horiguchi, K., Kohyama, T., Saitoh, M., Nagase, T., Miyazono, K., 2009. Thyroid transcription factor-1 inhibits transforming growth factor-β-mediated epithelial-to-mesenchymal transition in lung adenocarcinoma cells. Cancer Res., 69(7):2783–2791. [doi:10.1158/0008-5472.CAN-08-3490]PubMedCrossRefGoogle Scholar
- Yang, G.F., Xie, D., Liu, J.H., Luo, J.H., Li, L.J., Hua, W.F., Guan, X.Y., 2009. Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma. Gynecol. Oncol., 112(2):314–318. [doi:10.1016/j.ygyno.2008.10.024]PubMedCrossRefGoogle Scholar