miR-154 inhibits migration and invasion of human non-small cell lung cancer by targeting ZEB2.

Abstract

Emerging evidence suggests that microRNAs (miRs) play critical roles in the development and progression of non-small cell lung cancer (NSCLC). In a previous study, the present authors demonstrated that miR-154 acts as a tumor suppressor in NSCLC; however, its underlying molecular mechanism and target in NSCLC remain poorly understood. In the present study, ectopic expression of miR-154 remarkably suppressed cell migration and invasion in NSCLC cells. Zinc finger E-box binding homeobox 2 (ZEB2) was identified as a direct target of miR-154 in NSCLC cells. Furthermore, overexpression of miR-154 could decrease the expression of ZEB2 at the messenger RNA and protein levels. Ectopic expression of miR-154 also increased the levels of E-cadherin, an epithelial marker, and decreased the levels of vimentin, a mesenchymal marker, which contributed to suppress epithelial-mesenchymal transition (EMT) and to inhibit cell migration and invasion. In addition, downregulation of ZEB2 exerted similar effects to those caused by miR-154 overexpression on NSCLC cell migration and invasion, while upregulation of ZEB2 could significantly reverse the inhibitory effects on migration and invasion caused by miR-154 on NSCLC cells. These findings demonstrated that miR-154 inhibited migration and invasion of NSCLC cells by regulating EMT through targeting ZEB2, suggesting that miR-154 may be a potential anticancer therapeutic target for NSCLC.