MicroRNA-610 inhibits the migration and invasion of gastric cancer cells by suppressing the expression of vasodilator-stimulated phosphoprotein

Abstract 

Vasodilator-stimulated phosphoprotein (VASP) has been implicated in the establishment of cancerous phenotypes. However, the role of VASP in gastric cancer progression and metastasis remains poorly understood. Here, we demonstrated that VASP was upregulated by epidermal growth factor (EGF) and promoted the migration and invasion of gastric cancer cells. Then we explored the regulatory mechanisms responsible for high expression of VASP in gastric cancer. Based on miRNA expression profiling of the paired gastric cancer tissues and their adjacent non-tumour gastric tissues 18 miRNAs were identified including microRNA-610 (miR-610) which were down-regulated in gastric cancer. Next, we observed an inverse correlation between VASP and miR-610 expression levels in gastric cancer cells after EGF stimulation. Then we performed bioinformatics analysis, Western blot and reverse transcription polymerase chain reaction (RT-PCR) analysis and luciferase assay to establish that miR-610 directly targets VASP 3′-UTR and inhibits its expression. Functionally, we demonstrated that miR610-mediated inhibition of VASP expression resulted in a significant reduction in the migration and invasion properties of gastric cancer cells. The identification of miR-610 as a novel miRNA regulated by EGF that targets VASP in gastric cancer cells suggests that EGF-miR610-VASP axis may be exploited for therapeutic intervention to inhibit gastric cancer progression and metastasis.

Keywords: Gastric cancer, miR-610, VASP, Epidermal growth factor, Cell migration, Invasion, Metastasis