Tumor-suppressing effects of microRNA-612 in bladder cancer cells by targeting malic enzyme 1 expression.

Abstract

The present study investigated the possible tumor-suppressing function of microRNA (miR)-612 and the underlying molecular mechanism of its action in bladder cancer in vitro and in vivo. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was carried out to quantify the expression levels of miR-612 in bladder cancer tissues and cell lines. The data demonstrated that the level of miR-612 expression was significantly reduced in bladder cancer tissues and cell lines, as compared with that in non-cancerous tissues and cells. Reduced miR-612 expression was associated with advanced tumor, lymph node and metastasis stages, and with distant metastasis of bladder cancer. A functional study revealed that transfection of cells with an miR-612 mimic suppressed bladder cancer cell growth, colony formation, migration, invasion and epithelial-mesenchymal transition. Bioinformatics analysis identified that miR-612 targeted the expression of malic enzyme 1 (ME1), and this was confirmed by western blot and luciferase reporter assay results. Furthermore, the ME1 expression levels were inversely associated with miR-612 expression in bladder cancer tissue specimens. In addition, knockdown of ME1 expression using ME1 siRNA mimicked the effect of ectopic miR-612 overexpression in bladder cancer cells in terms of tumor cell growth, migration and invasion. By contrast, ME1 overexpression weakened the inhibitory effect of the miR-612 mimic in bladder cancer cells. In conclusion, the present study demonstrated that miR-612 may function as a tumor suppressor in bladder cancer by targeting ME1 expression.