MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2
MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2
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DOI：
10.1007/s11060-015-1753-x
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发表时间：
2015-05-01
影响因子：
3.9
通讯作者：
Guo, Zhenhui
中科院分区：
文献类型：
--
作者：
Sun, Jie;Zheng, Guodong;Guo, Zhenhui
提示microRNAs在多种癌症的发生发展中起着重要作用。在这里，我们发现miR-137在胶质母细胞瘤(GBM)细胞系中下调，并且miR-137的低水平与GBM患者预后不良的表型有关。异位表达miR-137可显著抑制GBM细胞的增殖和血管生成。此外，异位表达miR-137抑制了SCID小鼠异种移植模型中的肿瘤生长和血管生成。通过荧光素酶报告和Western印迹分析，确定EZH2是miR-137的直接靶点，过表达EZH2可以挽救miR-137对细胞增殖和血管生成的抑制作用。此外，来自GBM患者的肿瘤样本显示miR-137和EZH2水平呈负相关。我们的结果提示miR-137可能作为GBM的生物标志物，其活性的调节可能为GBM患者的治疗提供一种新的治疗策略。
It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients.