MicroRNA-18a inhibits cell growth and induces apoptosis in osteosarcoma by targeting MED27
MicroRNA-18a inhibits cell growth and induces apoptosis in osteosarcoma by targeting MED27
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DOI：
10.3892/ijo.2018.4374
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发表时间：
2018-07-01
影响因子：
5.2
通讯作者：
Li, Jiyu
中科院分区：
文献类型：
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作者：
Ding, Jing;Sha, Lin;Li, Jiyu
骨肉瘤（OS）是一种常见的恶性原发性骨肿瘤，已知OS患者对化疗的反应较差。微小RNA（miRNA或miR）是小的非编码RNA分子（长度约22个核苷酸），并且它们最近已成为关于它们在癌症治疗中的作用的研究主题。已有研究报道OS患者组织中miR-18 a的表达较正常组织显著降低。miR-18 a属于由宿主基因MIR 17 HG编码的miR-17-92簇。然而，miR-18 a在OS中的详细作用仍有待确定。在这项研究中，我们证明了miR-18 a模拟物抑制MG 63和Saos-2细胞的活力和迁移。流式细胞仪检测显示miR-18 a可诱导OS细胞凋亡。Western blot结果显示，miR-18 a下调Bcl-2和p-Akt的表达，上调caspase-3和Bax的表达。此外，我们通过双荧光素酶分析证明了介体复合物亚基27（MED 27）是miR-18 a的靶点。最后，来自体内实验的数据表明，小鼠中的肿瘤生长被miR-18 a模拟物显著抑制，伴随着Ki 67阳性细胞百分比的降低，以及MED 27和p-Akt蛋白表达水平的下调。本研究的发现可能有助于阐明miR-18 a的功能，特别是其在OS细胞凋亡调控中的作用，并表明MED 27可能是治疗OS的潜在新靶点。
Osteosarcoma (OS) is a common malignant primary bone tumor and patients with OS are known to have a poor response to chemotherapy. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules (approximately 22 nucleotides in length) and they have recently become a topic for research as regards their role in cancer therapeutics. Previous studies have reported miR-18a expression in patients with OS is significantly decreased compared with that in normal adjacent tissue. miR-18a belongs to the miR-17-92 cluster encoded by the host gene MIR17HG. However, the detailed role of miR-18a in OS remains to be determined. In this study, we demonstrated that miR-18a mimics inhibited MG63 and Saos-2 cell viability and migration. In addition, flow cytometry assay revealed that miR-18a induced OS cell apoptosis. Western blot analysis indicated that the expression levels of Bcl-2 and p-Akt were downregulated, while the levels of cleaved caspase-3 and Bax proteins were upregulated by miR-18a. Moreover, we demonstrated that mediator complex subunit 27 (MED27) was the target of miR-18a through dual luciferase assay. Finally, data from in vivo experiments indicated that tumor growth in mice was significantly suppressed by miR-18a mimics, accompanied by a decrease in the percentage of Ki67-positive cells, and by the downregulation in MED27 and p-Akt protein expression levels. The findings of the present study may aid in the clarification of the function of miR-18a, particularly as regards its role in the regulation of OS cell apoptosis, and indicate that MED27 may be a potential novel therapeutic target in the treatment of OS.