Radiation exposure triggers the malignancy of non-small cell lung cancer cells through the activation of visfatin/Snail signaling

It is estimated that one-half of patients with non-small cell lung cancer (NSCLC) undergo radiotherapy worldwide. However, the outcome of radiotherapy alone is not always satisfactory. The aim of the present study was to evaluate the effects of radiotherapy on the malignancy of NSCLC cells. It was demonstrated that radiation therapy could increase the migration and invasion of NSCLC cells in vitro. Moreover, the upregulation of visfatin, a 52-kDa adipokine, mediated radiation-induced cell motility. A neutralizing antibody specific for visfatin blocked radiation-induced cell migration. Radiation and visfatin induced the expression of Snail, a key molecule that regulates epithelial to mesenchymal transition in NSCLC cells. Furthermore, visfatin positively regulated the mRNA stability of Snail in NSCLC cells, but had no effect on its protein degradation. This may be explained by visfatin-mediated downregulation of microRNA (miR)-34a, which was shown to bind the 3′ untranslated region of Snail mRNA to promote its decay. Collectively, these findings suggested that radiation could induce cell motility in NSCLC cells through visfatin/Snail signaling.