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Background  Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in many cancers. However, the role of MiRNA in FN assembly-related ESCC mobility remains unexplored.    Methods  We divided ESCC CE81T cells into high-FN assembly (CE81 FN+ ) and low-FN assembly (CE81 FN− ) groups by flow cytometry. MiRNA microarray analysis identified  miR-146a  expression as the most down-regulated miRNA in comparison of CE81 FN+  and CE81 FN−  cells.    Results  Cell proliferation and migration were decreased when CE81 FN+  cells overexpressed transgenic  miR-146a  compared to the parental cells, indicating an inverse correlation between low  miR-146a  expression and high proliferation as well as motility of FN assembly ESCC cells. Furthermore, vimentin is the target gene of  miR-146a  involved in ESCC tumorigenesis.  MiR-146a  suppressed cell proliferation, migration and invasion of CE81 FN+  cells through the inhibition of vimentin expression, as confirmed by real-time PCR, Western blotting and Transwell™ assay. Analysis of one hundred and thirty-six paired ESCC patient specimens revealed that low  miR-146a  and high vimentin levels were frequently detected in tumor, and that the former was associated with late tumor stages (III and IV). Notably, either low  miR-146a  expression or high vimentin level was significantly associated with poor overall survival rate among ESCC patients.    Conclusions  This is the first report to link FN assembly in the cell membrane with  miR-146a , vimentin and ESCC tumorigenesis both in vitro and in ESCC patients.

MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly