Aberrant expression of miRNAs is involved in several carcinogenic processes, including tumor growth, metastasis and angiogenesis. The aim of this study was to determine the role of miR-218 in gastric cancer angiogenesis. In situ hybridization was performed on a set of tissue microarray samples to assess the difference in miR-218 expression in vessels between tumor tissues and normal gastric mucosa. In vitro, ectopic expression of miR-218 disturbed the tubular structure and inhibited the migration of endothelial cells. Motility and tube formation were rescued when miR-218 was downregulated. Moreover, miR-218 suppressed endothelial cell sprouting in a fibrin bead sprouting assay. Subsequently, we identified ROBO1 as a target of miR-218 in endothelial cells and determined it was responsible for the effect of miR-218 on tumor angiogenesis. In vivo, local injection of mature miR-218 in xenografted tumors disrupted the vessel plexus and thus inhibited tumor growth. Taken together, our study demonstrated an anti-angiogenic role of miR-218 in gastric cancer and indicated that delivery of miR-218 may be a potential therapeutic strategy to inhibit tumor angiogenesis.
Keywords: Angiogenesis; Gastric cancer; In situ hybridization; ROBO1; miR-218.
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