Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RAR alpha fusion protein. We have previously found that PML-RAR alpha-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is down regulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL (C) 2016 Elsevier Inc. All rights reserved.