Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation
Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation
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鉴定参与急性早幼粒细胞白血病细胞增殖的 miR-125b 靶标
DOI：
10.1016/j.bbrc.2016.09.020
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发表时间：
2016-09-30
影响因子：
3.1
通讯作者：
Li, Yangqiu
中科院分区：
文献类型：
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作者：
Zhang, Yikai;Zeng, Chengwu;Li, Yangqiu
急性早幼粒细胞白血病（APL）的特征在于PML-RAR α融合蛋白的存在。我们以前发现PML-RAR α调控的miR-125 b在APL中高度表达;然而，miR-125 b参与APL增殖的调控作用和机制的特征尚未阐明。在本研究中，我们证明miR-125 b促进APL细胞的增殖与PI 3 K/Akt和MAPK信号通路的参与。此外，我们鉴定了BTG 2、MAP 3 K11、RPS 6 KA 1和PRDM 1作为miR-125 b的推定靶点，我们使用荧光素酶报告基因构建体验证了这一点。此外，我们证明了miR-125 b靶点的表达在APL患者的白血病细胞中下调。因此，我们的研究结果提供了证据，证明miR-125 b可以调节多种致癌细胞增殖途径，并可能成为APL（C）2016 Elsevier Inc. All rights reserved.
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.