Role of miR-497 in VEGF-A-mediated cancer cell growth and invasion in non-small cell lung cancer

Abstract

The malignancy of non-small cell lung cancer (NSCLC) is largely due to its invasion. Hence, prevention of the cancer cell invasion, which is essentially regulated by vascular endothelial growth factor A (VEGF-A), is substantially critical for a successful treatment for NSCLC. Here, we showed that compared to other cancers, NSCLC had a significant higher ratio of VEGF-A protein vs mRNA, and significantly lower levels of miR-497, suggesting presence of a post-transcriptional control of VEGF-A in NSCLC different from other cancers. Compared with paired normal lung tissue, NSCLC expressed lower levels of miR-497 and higher levels of VEGF-A. Moreover, the levels of miR-497 and VEGF-A were inversely correlated in NSCLC specimen. Bioinformatics analyses showed that miR-497 bound to 3′-UTR of VEGF-A mRNA in NSCLC lines to inhibit its translation. Overexpression of miR-497 in NSCLC lines decreased VEGF-A protein, while depletion of miR-497 in NSCLC lines increased VEGF-A protein. However, modification of miR-497 levels in NSCLC lines did not alter VEGF-A mRNA levels. Overexpression of miR-497 in NSCLC lines inhibited cell growth and invasion, while depletion of miR-497 in NSCLC lines increased cell growth and invasion. Together, our data demonstrate a previously unappreciated role for miR-497 in suppression of VEGF-A-mediated NSCLC cancer cell growth and invasion.