Yu_2020_Cancer.Biomark_27_471

BACKGROUND: Gastric cancer is one of the leading causes of death worldwide. MicroRNA-30a (miR-30a) has been demonstrated to be involved in several types of cancer development. OBJECTIVE: We aimed to identify the molecular mechanism of miR-30a in gastric cancer. METHODS: We investigated the expression of miR-30a in gastric cancer tissues by qRT-PCR. The role of miR-30a on the metastasis and proliferation of gastric cancer was evaluated by cell migration assay, CCK-8 assay and tumor peritoneal dissemination model. The target of miR-30a in gastric cancer was identified. RESULTS: We discovered that miR-30a was significantly downregulated in gastric cancer tissues compared with adjacent nonmalignant tissues. The expression of miR-30a was inversely correlated with progression of gastric cancer. Gain- and loss-of function revealed that miR-30a acted as a potent tumor suppressor in gastric cancer. Re-expressed miR-30a inhibited gastric cancer cells migration, knock down miR-30a have the opposite effects. Furthermore, overexpression of miR-30a suppressed tumor peritoneal dissemination in vivo. We identified that fibroblast activation protein alpha (FAPalpha) was a direct target of miR-30a. The relative expression of FAPalpha was significantly higher in gastric cancer tissues compared with adjacent nonmalignant tissues. Inhibition of FAPalpha could recapitulate the effects of miR-30a, and overexpression of FAPalpha could abrogate the effect of miR-30a. CONCLUSION: MiR-30a inhibited gastric cancer metastasis by targeting FAPalpha, suggesting that miR-30a may function as a novel tumor suppressor in gastric cancer.