MicroRNA-141 inhibits migration of gastric cancer by targeting zinc finger E-box-binding homeobox 2

摘要

Human microRNA (miR)-141 is a member of the miR-200 family, which has been reported to be downregulated in gastric cancer, and involved in the proliferation of gastric cancer cells. However, little is currently known regarding its role in the migration of gastric cancer. The present study investigated the function of miR-141 in gastric cancer cell migration, and evaluated the contribution of zinc finger E-box-binding homeobox 1 and 2 (ZEB1/2) in miR-141 mediated migration of gastric cancer cells. The expression levels of miR-141 and its potential ZEB1/2 targets were examined by quantitative polymerase chain reaction (qPCR) and western blotting, respectively. The migration of SGC-7901 and HGC-27 gastric cancer cells, which had been transfected with an miRNA precursor, was examined by cell migration and wound healing assays. A luciferase activity assay was used to validate whether ZEB1/2 was a direct target of miR-141. The results demonstrated that overexpression of miR-141 markedly inhibited the migration of gastric cancer cells in vitro. Forced overexpression of miR-141 significantly reduced the luciferase activity of the 3′-untranslated region of ZEB2 in gastric cancer cells. Furthermore, the mRNA and protein expression levels of ZEB2 were reduced in cells overexpressing miR-141, whereas the protein expression levels of E-cadherin were increased. In gastric tumor samples the expression levels of ZEB2 were inversely correlated with the expression of miR-141. These results suggest that miR-141 may be involved in the inhibition of gastric cancer cell migration, and that ZEB2 is a target gene of miR-141.