We investigated the possible association between DLKI gene promoter region methylation and the increased invasion capacity of non-small cell lung cancer (NSCLC). Lung cancer cell line H1299, as well as the gene transfection and RNA interference technology were used to build DLK gene overexpression and knockdown cells. An in vitro invasion assay was performed to observe the changes in the invasion ability of lung cancer cells. Western blot analysis was used to verify Notchl and matrix metalloproteinase-9 (MMP-9) expression levels and a sulfurous acid sequencing technique was used to test the DNA methylation level in the promoter region. Our results showed that the invasion ability of cells in the overexpression group was significantly enhanced. This ability was considerably reduced in the knockdown group. The Notchl and MMP-9 expression level increased significantly in the overexpression group, while it was reduced considerably in the knockdown group. We detected significantly lower levels of DNA methylation in the promoter region in the overexpression group. It was concluded that methylation of the DLK1 gene promoter region increased the invasion ability of NSCLC. Furthermore, it is possible that this process is related to the Notch signaling pathway.
Keywords: DLK1 gene; DNA methylation in promoter region; Notch; invasion ability; matrix metalloproteinase-9; non-small cell lung cancer.