Downregulation of RIKP by miR-200a promotes the invasive ability of esophageal cancer cells by upregulating the expression of LIN28 and MMP-14.

Esophageal cancer (EC) is one of common digestive tract malignant tumors which morbidity and mortality were increased year by year. This study was aimed to investigate the role of microRNA (miR)-200a in EC. Human esophageal squamous cell carcinoma (ESCC) cells TE3 was transfected with miR-200a mimic or scramble control. Cell viability and invasion were assessed by MTT and Transwell assay, respectively. Binding effect of miR-200a on 3'UTR of RKIP was verified by luciferase activity assay. RKIP expression in miR-200a mimic transfected cells was measured. RKIP was overexpressed in miR-200a transfected cells and cell viability and invasion were measured. The expressions of Raf1, ERK, MMP-14, LIN28 and GRK-2 were also measured by qRT-PCR and Western blot analysis, respectively. Results showed that miR-200a mimic transfection increased cell viability and invasion of TE3 cells in vitro. miR-200a binding with 3'UTR of RKIP negatively regulated RKIP expression. RKIP overexpression inhibited effects of miR-200a on cell viability and invasion, as well as the increased phosphorylation levels of Raf1 and ERK. miR-200a increased expressions of MMP-14, LIN28 and GRK-2 in TE3 cells, and the up-regulations were inhibited by RKIP overexpression. In conclusion, the up-regulation of miR-200a in TE3 cells promoted cell viability and invasion via negatively regulating RKIP expression. RKIP was a direct target of miR-200a. miR-200a might be involved in activation of MAPK/ERK signaling pathway and expression of MMP-14, LIN28 and GRK-2 which were important factors of intracellular information transduction. Our findings demonstrated that miR-200a regulated ESCC cells via regulating RKIP expression. IJCEP