693197

MIR612

Previous research showed that microRNA-612 (miR-612) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of hepatocellular carcinoma (HCC). AKT2 was confirmed to be a direct target of miR-612, through which the epithelial-mesenchymal transition (EMT) and metastasis of HCC were inhibited. Our present findings reveal that miR-612 is able to suppress the stemness of HCC by reducing the number and size of tumorspheres as well as clone formation in soft agar, and to relieve drug resistance to cisplatin and 5-fluorouracil. In addition, miR-612 hampered the capacity of tumorigenesis in NOD/SCID mice and redistributed the tumor invasive frontier of miR-612-modulating cells. Finally, our findings suggest that Wnt/beta-catenin signaling is required in the regulation of EMT-associated stem cell-like traits by miR-612.CI - Copyright (c) 2014 Elsevier Inc. All rights reserved.

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 transcriptionquantitative polymerase chain reaction (RTqPCR) was carried out to quantify the expression levels of miR612 in bladder cancer tissues and cell lines. The data demonstrated that the level of miR612 expression was significantly reduced in bladder cancer tissues and cell lines, as compared with that in noncancerous tissues and cells. Reduced miR612 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 miR612 mimic suppressed bladder cancer cell growth, colony formation, migration, invasion and epithelial-mesenchymal transition. Bioinformatics analysis identified that miR612 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 miR612 expression in bladder cancer tissue specimens. In addition, knockdown of ME1 expression using ME1 siRNA mimicked the effect of ectopic miR612 overexpression in bladder cancer cells in terms of tumor cell growth, migration and invasion. By contrast, ME1 overexpression weakened the inhibitory effect of the miR612 mimic in bladder cancer cells. In conclusion, the present study demonstrated that miR612 may function as a tumor suppressor in bladder cancer by targeting ME1 expression.