Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation

• Published in: Biochemical and biophysical research communications 2016-09, Vol.478 (4), p.1758-1763
• Main Authors: Zhang, Yikai, Zeng, Chengwu, Lu, Shuai, Qin, Tianyu, Yang, Lijian, Chen, Shaohua, Chen, Jie, Li, Yangqiu
• Format: Article
• Language: English
• Subjects: 3′-untranslated regions; 60 APPLIED LIFE SCIENCES; Acute promyelocytic leukemia; Adolescent; Adult; Blotting, Western; Cell Line, Tumor; CELL PROLIFERATION; Cell Proliferation - genetics; Female; Gene Expression Regulation, Leukemic; Humans; Immediate-Early Proteins - genetics; LEUKEMIA; Leukemia, Promyelocytic, Acute - genetics; Leukemia, Promyelocytic, Acute - metabolism; Leukemia, Promyelocytic, Acute - pathology; LUCIFERASE; Male; MAP Kinase Kinase Kinases - genetics; MAP Kinase Signaling System - genetics; MicroRNAs; MicroRNAs - genetics; Middle Aged; Mitogen-Activated Protein Kinase Kinase Kinase 11; PATIENTS; Phosphatidylinositol 3-Kinases - metabolism; PML-RARα; Positive Regulatory Domain I-Binding Factor 1; PROLIFERATION; Repressor Proteins - genetics; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Protein S6 Kinases, 90-kDa - genetics; RNA; SIGNALS; Small non-coding RNAs; Tumor Suppressor Proteins - genetics; Young Adult
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.09.020

Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-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 downregulated 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. •miR-125b promotes cell proliferation by AKT and MAPK signaling pathways.•miR-125b target to MAP3K11,BTG2, RPS6KA1 and PRDM1.•MAP3K11,BTG2, RPS6KA1 and PRDM1 were dowregulated by miR-125b in NB4 and primary cells from APL patients.