MiR-486-5p inhibits metastasis by targeting neuropilin-2 in gastric cancer

Previous studies have revealed that aberrant expressions of miRNAs participate in almost every step of carcinogenesis. Despite of large numbers of miRNAs disclosed, the function of miR-486-5p in the metastasis of gastric cancer is not elucidated so far. In the current study, we collected 65 gastric cancer samples and adjacent tissues to detect the miR-486-5p expression using qPCR, and applied luciferase reporter assay to verify the effect of miR-486-5p on the transcriptional activity of the Neuropilin-2 (NRP2) mRNA 3'UTR. Xenograft model was performed to test the effect of miR-486-5p on gastric cancer cell proliferation and metastatic ability in nude mice. Immunohistochemistry were used to confirm the relationship between NRP2 and lymphatic vessel density in these gastric cancer samples. Our results found that expression of MiR-486-5p was obviously decreased in the gastric cancer samples compared with the adjacent samples (P<0.01). Ectopic overexpression of miR-486-5p significantly inhibited the transcriptional activity and expression level of NRP2, as detected by luciferase and western blot, respectively. Furthermore, the gastric cancer cell SGC-7901 transfected with miR-486-5p showed obvious low tumorigenesis ability compared with the non-target control in the nude mice xenograft model (p<0.01). In xenograft tissues the expression of NRP2 had a positive correlation with the LYVE-1 expression, suggesting NRP2 promote lymphangiogenesis. Thus, our findings demonstrated that miR-486-5p function as a tumor suppressor in gastric cancer cell proliferation and lymphangiogenesis via targeting NRP2, and suggesting miR-486-5p a new potential target for developing diagnostics and therapy strategy in gastric cancers.