MicroRNA-107 promotes migration and invasion of gastric cancer cells by targeting Notch2

Abstract

Objective To detect the expression of microRNA-107 (miR-107) in gastric cancer cells and its molecular mechanism for regulating migration and invasion of gastric cancer cells. Methods The expression levels of miR-107 and Notch2 mRNA in gastric cancer MKN45 cells and gastric epithelial cells GES-1 were detected using real-time PCR. MKN45 cells were transfected with a miR-107 inhibitor and the changes in cell migration and invasion were detected with Transwell assay. In MKN45 cells transfected with a Notch2-overexpressing plasmid, the changes in cell migration and invasion and the expression of matrix metalloproteinase-9 (MMP-9) were detected using Transwell assay, real-time PCR and Western blotting, respectively. Targetscan online prediction and dual-luciferase assay were used to analyze the relationship between miR-107 and Notch2. The changes in the migration and invasion of MKN45 cells after inhibiting miR-107 and Notch2 silencing were investigated using Transwell assay. Results Compared with those in GES-1 cells, the expression of miR-107 was significantly up-regulated (P < 0.01) and Notch2 was significantly down-regulated (P < 0.01) in MKN45 cells. Both inhibition of miR-107 and overexpression of Notch2 significantly attenuated the migration and invasion abilities of MKN45 cells (P < 0.01). Overexpression of Notch2 significantly promoted the expressions of MMP-9 mRNA and protein in the cells (P < 0.01). The results of Targetscan online prediction and dual-luciferase assay showed that Notch2 was potentially the target gene of miR-107 (P < 0.01), and inhibiting miR-107 promoted the expression of Notch2. Silencing Notch2 in MKN45 cells obviously reversed miR-107-induced inhibition of cell migration and invasion. Conclusion The expression of miR-107 is up-regulated in gastric cancer cells. MiR-107 enhances the expression of MMP-9 by targeting Notch-2 to promote the migration and invasion of gastric cancer cells.

Keywords

• microrna-107
• notch2
• gastric cancer
• cell migration
• neoplasm invasiveness