MiR‐2392 suppresses metastasis and epithelial–mesenchymal transition by targeting <i>MAML3</i> and <i>WHSC1</i> in gastric cancer

Abstract

MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis <i>in vitro</i> and <i>in vivo</i> We identified <i>MAML3</i> and <i>WHSC1</i> as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survival in patients with GC. Furthermore, forced expression of miR-2392 substantially suppressed Slug and Twist1, transcriptional repressors of E-cadherin, by targeting <i>MAML3</i> and <i>WHSC1</i>, respectively, resulting in inhibition of the epithelial-mesenchymal transition. These findings indicate that the miR-2392-<i>MAML3</i>/<i>WHSC1</i>-<i>Slug</i>/<i>Twist1</i> regulatory axis plays a critical role in GC metastasis. Restoration of miR-2392 may be a therapeutic approach for blocking GC metastasis.-Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F., Zhao, X., Nie, Y., Fan, D. MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting <i>MAML3</i> and <i>WHSC1</i> in gastric cancer.