Downregulated microRNA-200a promotes EMT and tumor growth through the Wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma

In a previous study, we found that microRNA (miRNA)-200a suppresses Wnt/β-cateninsignaling by interacting with β-catenin, thereby inhibiting migration, invasionand proliferation. However, the mechanism involved in this suppression remainsunclear. In the present study, we investigated the underlying mechanism of miR-200aregulation of epithelial-mesenchymal transition (EMT) in gastric carcinoma cells,and confirmed the tumor suppressor role of miR-200a in vivo. The expressions ofmiRNA-200a, -200b and -200c, identified by fluorescent in situ hybridization,were downregulated and inversely correlated with WHO grades of gastric adenocarcinoma(GA). The expression of the potential miR-200a target genes ZEB1 and ZEB2 wasdetected immunohistochemically. These examinations used the same tissue microarraysto analyze the relationships between miR-200a and potential target genes. Theexpression of miR-200a and ZEB1/ZEB2 in the same GA tissue microarrays was inverselyrelated. Restored miR-200a expression inhibited tumor growth in nude mice harboringsubcutaneous SGC7901 xenografts. The expression of N-cadherin, β-catenin, Twist1and Snail2 decreased, and E-cadherin levels increased, when miR-200a was elevated,as tested by fluorescence microscopy and immunohistochemistry. Similar resultswere observed in vivo. We found upregulated miR-200a expression to increase E-cadherinand suppress the Wnt/β-catenin pathway by targeting ZEB1 and ZEB2 in GA, thusdelaying tumor growth in vivo. The effect of miR-200a on Wnt/β-catenin signalingmay provide a therapeutic target against EMT.