Identification of miR-4510 as a metastasis suppressor of gastric cancer through regulation of tumor microenvironment via targeting GPC3.

The genes miR-4510 and glypican-3 (GPC3) have reported to be closely associated with tumors, with miR-4510 inversely correlated with GPC3 mRNA and protein in hepatocellular carcinoma samples. Glypican-3-expressing gastric cancer (GPC3-GC), characterized as gastric cancer (GC) expressing GPC3, accounts for 11% of the GC cases. However, the expression and mechanism of action of miR-4510 in GPC3-GC have not been clearly defined. We found that miR-4510 expression in GC tissues was significantly lower than that in the adjacent tissues (p < 0.001). miRNA-4510 expression in GPC3-GC was significantly lower than that in GPC3-negative GC tissue (p < 0.001). Our study confirmed that miR-4510 is inversely correlated with GPC3 in gastric cancer samples and that GPC3 is a direct target gene of miR-4510. The proportion of M2 macrophages in GC with low expression of miR-4510 was significantly increased, while the proliferation of CD8+ T cells was limited. miR-4510 may change the immunosuppressive signals in the tumor microenvironment by downregulating GPC3 and inhibiting gastric cancer cell metastasis. Oxaliplatin treatment may become a specific therapeutic drug for patients with miR-4510 inhibition and GPC3-GC.