MiR-15a/16 regulates the growth of myeloma cells, angiogenesis and antitumor immunity by inhibiting Bcl-2, VEGF-A and IL-17 expression in multiple myeloma

MiR-15a/16 regulates the growth of myeloma cells, angiogenesis and antitumor immunity by inhibiting Bcl-2, VEGF-A and IL-17 expression in multiple myeloma
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MiR-15a/16通过抑制多发性骨髓瘤中Bcl-2、VEGF-A和IL-17的表达来调节骨髓瘤细胞的生长、血管生成和抗肿瘤免疫

DOI:
10.1016/j.leukres.2016.08.013
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发表时间:
2016-10-01
期刊:
影响因子:
2.7
通讯作者:
Li, Zhenyu
Li, Zhenyu
中科院分区:
医学3区
文献类型:
--
作者:
Li, Yanjie;Zhang, Bingyun;Li, Zhenyu

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已经报道miRNA参与许多癌症的发病机制。本文探讨了miR-15 a/16在多发性骨髓瘤(MM)发病中的作用及其机制。我们发现miR-15 a/16在初诊MM患者的骨髓来源的单个核细胞(BM-MNCs)中下调,并且miR-15 a/16的下调与国际分期系统(ISS)分期相关。结果表明,miR-15 a/16可抑制骨髓瘤细胞增殖,并通过抑制抗凋亡蛋白Bcl-2的表达,提高U266细胞的凋亡率。我们还发现miR-15 a/16可以降低骨髓瘤细胞培养上清中VEGF-A和IL-17的水平。这些结果表明,miR-15 a/16可能通过多种调节机制在MM中发挥肿瘤抑制剂的作用,它们可能是MM治疗的潜在靶点。(C)2016 Elsevier Ltd.保留所有权利。
miRNAs have been reported to be involved in the pathogenesis of many cancers. In this article, we investigated the role and the mechanisms of miR-15a/16 in the pathogenesis of multiple myeloma (MM). We found that miR-15a/16 was down-regulated in bone marrow-derived mononuclear cells (BM-MNCs) of newly diagnosed patients with MM and the downregulation of miR-15a/16 was correlated with International Staging System (ISS) stage. We then demonstrated miR-15a/16 inhibited myeloma cells proliferation, and increased apoptosis rate of U266 cells by suppressing the expression of anti-apoptosis protein Bcl-2. We also found miR-15a/16 could decrease VEGF-A and IL-17 levels in the supernatant of myeloma cells. These results indicate that miR-15a/16 may function as a tumor suppressor in MM through multiple regulatory mechanisms and they may be potential targets for the therapy of MM. (C) 2016 Elsevier Ltd. All rights reserved.