Lentivirus-mediated overexpression of miR-124 suppresses growth and invasion by targeting JAG1 and EZH2 in gastric cancer

Abstract

MicroRNA-124 (miR-124) expression is downregulated and has a tumor suppressor role in various types of cancer. The present study revealed that genes encoding miR-124 were frequently methylated and the expression of miR-124 was downregulated in gastric cancer tissues. Stable expression of miR-124 using a lentiviral vector inhibited gastric cancer cell growth, migration and invasion in vitro. In addition, overexpression of miR-124 suppressed gastric cancer cell xenograft growth in nude mice. The expression of the Notch ligand Jagged1 (JAG1) and enhancer of zeste homolog 2 (EZH2) was downregulated upon miR-124 overexpression, and silencing of JAG1 or EZH2 by RNA interference also suppressed gastric cancer cell growth, migration and invasion. Furthermore, expression of fibronectin and vimentin, not able elements of the epithelial-mesenchymal transition, were suppressed by overexpression of miR-124 or inhibition of JAG1 or EZH2 expressions in GC. Together, these results indicated that miR-124 suppressed gastric cancer progression, partly through inhibiting JAG1 and EZH2. Thus, lentivirus-mediated overexpression of miR-124 may be a potential therapeutic strategy against gastric cancer.