MicroRNA-212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells

As a tumor-associated microRNA (miR), miR-212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR-212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus-mediated gain-of-function demonstrated promotion of ESCC cell migration and invasion when miR-212 was overexpressed, and no effect on cell proliferation. miR-212 resulted in downregulation of the expression of E-cadherin, β-catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase-9 and urokinase-type plasminogen activator. Furthermore, berberine inhibited miR-212-induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5-(Tetradecyloxy)-2-furoic acid (TOFA; an acetyl-CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR-212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial-mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR-212.