MiR-451 suppresses proliferation, migration and promotes apoptosis of the human osteosarcoma by targeting macrophage migration inhibitory factor
MiR-451 suppresses proliferation, migration and promotes apoptosis of the human osteosarcoma by targeting macrophage migration inhibitory factor
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MIR-451靶向巨噬细胞移动抑制因子抑制骨肉瘤细胞增殖、迁移和促进细胞凋亡
DOI：
10.1016/j.biopha.2016.12.121
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发表时间：
2017-03-01
影响因子：
7.5
通讯作者：
Yu, Bin
中科院分区：
文献类型：
--
作者：
Liu, Wei;Liu, Sheng-Yao;Yu, Bin
以往的研究表明，MIR-451在人骨肉瘤的癌变过程中起着重要作用，但MIR-451影响骨肉瘤的潜在机制尚不完全清楚。本研究旨在揭示MIR-451发挥肿瘤抑制作用的机制。实时荧光定量聚合酶链式反应检测MIR-451在骨肉瘤组织和骨肉瘤细胞系中的表达。用四甲基偶氮唑盐比色法和细胞周期分析法检测细胞的增殖能力。用迁移实验和流式细胞仪分别检测细胞的迁移和凋亡情况。此外，通过试管形成实验检测了MIR-451模拟物对HUVEC细胞血管生成的影响。用荧光素酶和Western印迹法检测MIR-451对MIF的影响。结果表明，与正常骨组织相比，骨肉瘤组织中MIR-451的表达水平显著降低。MIR-451过表达显著抑制骨肉瘤细胞的增殖和迁移，并诱导骨肉瘤细胞凋亡。此外，还检测了MIR-451模拟物对HUVEC细胞血管生成的影响，并检测到与对照组相比，MIR-451模拟物对血管生成能力的影响。最后，我们证明了MIR-451过表达通过下调MIF而抑制骨肉瘤的恶性行为。这些发现表明，MIR-451可能在骨肉瘤中起到肿瘤抑制作用。MIR-451通过抑制MIF的表达，抑制骨肉瘤细胞的增殖、迁移和血管生成，促进骨肉瘤细胞的凋亡。MIR-451/MIF可能成为治疗骨肉瘤的新靶点。(C)2016年，由爱思唯尔·马森公司出版。
Previous studies have shown that MiR-451 plays an important role in human osteosarcoma carcinogenesis, but the underlying mechanism by which MiR-451 affects the osteosarcoma has not been fully understood. This study intends to uncover the mechanism by which MiR-451 functions as a tumor suppressor. The expression of MiR-451 in osteosarcoma tissues and osteosarcoma cell lines was monitored by real-time PCR. The proliferation ability was examined by MTT and cell cycle assay. The migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. Moreover, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was examined by tube formation assay. The effect of MiR-451 on MIF was determined by luciferase assays and Western blot assay. The results showed that MiR-451 expression level was significantly reduced in the osteosarcoma compared with normal bone tissues. Overexpression of MiR-451 significantly attenuated the proliferation and migration, and induced the apoptosis of osteosarcoma cells. Furthermore, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. Finally, we demonstrated that MiR-451 overexpression inhibited the malignant behavior of osteosarcoma by downregulating MIF. These findings suggest that MiR-451 may act as a tumor suppressor in osteosarcoma. MiR-451 inhibited cell proliferation, migration and angiogenesis and promoted apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of MIF. MiR-451/MIF may be a novel therapeutic target in treatment of osteosarcoma. (C) 2016 Published by Elsevier Masson SAS.