MicroRNA-625-3p inhibits gastric cancer metastasis through modulating EZH2.

Abstract

The aim of this study was to investigate whether microRNA-625-3p participated in the malignant progression of gastric cancer and inhibited GCa metastasis by regulating EZH2 (Enhancer of zeste homolog 2). Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of microRNA-625-3p in 36 pairs of GCa tissues and para-cancerous tissues. The interplay between microRNA-625-3p level and clinical indexes or prognosis of GCa patients was analyzed. MicroRNA-625-3p mimics and inhibitors, as well as their negative controls, were transfected into GCa cell lines to establish microRNA-625-3p overexpression and down-regulation models in vitro, respectively. QRT-PCR was applied to further verify the transfection efficiency. Cell counting kit-8 (CCK-8), colony formation, and transwell assays were performed to analyze the impact of microRNA-625-3p on the proliferative and invasiveness abilities of GCa AGS and SGC-7901 cells. Finally, the regulatory mechanism of microRNA-625-3p on the downstream gene EZH2 was explored by cell reverse experiment. QRT-PCR results revealed that microRNA-625-3p expression level in GCa tissues was remarkably lower than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with high expression of microRNA-625-3p, the incidence of lymph node or distant metastasis was significantly higher in patients with low expression of miR-625-3p, whereas the overall survival rate was lower (p<0.05). Compared with GCa cells in NC inhibitor group, the proliferative ability and invasiveness of cells in microRNA-625-3p inhibitor group were remarkably promoted (p<0.05). However, the opposite results were observed in microRNA-625-3p mimics group. Our findings further demonstrated that the expression of EZH2 increased remarkably in GCa cell lines and tissues (p<0.05). Meanwhile, its expression level was negatively correlated with microRNA-625-3p level. Cell reverse experiment showed that EZH2 could offset the influence of microRNA-625-3p on the proliferation and metastasis GCa cells, thereby affecting the malignant progression of GCa. MicroRNA-625-3p was remarkably correlated with lymph node or distant metastasis and poor prognosis of GCa patients. In addition, microRNA-625-3p might inhibit the malignant progression of GCa via modulating EZH2.