RESUMO
Chronic myeloid leukemia (CML) is a type of malignant tumor characterized by the accumulation of a large number of immature white blood cells in the blood and bone marrow. BAK1 was predicted to be the target gene of microRNA-451 (miR-125b). The present study was designed to illustrate the mechanism of miR-125b in regulating CML via targeting BAK1. In this study, we found that the expression of miR-125b increased strongly, whereas the expression of BAK1 decreased significantly in CML patients and CML cell lines compared with healthy controls. Moreover, the luciferase report assay confirmed the interaction between miR-125b and BAK1 mRNA. After transfection of the miR-125b mimic or miR-125b inhibitor into CML cells, we found that the inhibition of miR-125b decreased the proliferation rates and promoted apoptosis with cell cycle arrest at the G0/G1 phase in both K562 and NB-4 cells, increased the expression of BAK1 and Caspase-3, and decreased the expression of Bcl-2 and c-myc; the miR-125b mimic yielded the opposite results. In addition, siBAK1 offset the suppression effect of the miR-125b inhibitor in K562 cells, indicating that miR-125b promotes these cellular processes by inhibiting the expression of BAK1. Further in vivo experiments supported these findings because miR-125b suppression reduced CML growth in mice. Taken together, our study suggests that the down-regulation of miR-125b affects the expression of BAK1, promotes cell apoptosis and inhibits cell proliferation, leading to up-regulated expression of pro-apoptosis factors, down-regulated expression of anti-apoptosis factors in the mitochondrial apoptotic pathway, and decreased tumor size and weight of CML in vivo. These results provide a potential therapeutic strategy for CML.