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微小RNA-137通过靶向EZH2抑制人胶质母细胞瘤细胞的增殖和血管生成。

MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2.

作者信息

Sun Jie, Zheng Guodong, Gu Zhengtao, Guo Zhenhui

机构信息

Medical Intensive Care Unit of Guangzhou General Hospital of Guangzhou Military Command; Guangdong Provincial Key Laboratory of Geriatric Infection and Organ Function Support & Guangzhou Key Laboratory of Geriatric Infection and Organ Function Support, Guangzhou, People's Republic of China.

出版信息

J Neurooncol. 2015 May;122(3):481-9. doi: 10.1007/s11060-015-1753-x. Epub 2015 May 5.

Abstract

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.

摘要

有人提出,微小RNA在各种癌症的发展中发挥重要作用。在此,我们表明,miR-137在胶质母细胞瘤(GBM)细胞系中表达下调,且低水平的miR-137与GBM患者的不良预后表型相关。miR-137的异位表达显著抑制GBM细胞增殖和血管生成。此外,在SCID小鼠异种移植模型中,miR-137的异位表达抑制肿瘤生长和血管生成。通过荧光素酶报告基因和蛋白质印迹分析,EZH2被鉴定为miR-137的直接靶点,且EZH2过表达可挽救miR-137对细胞增殖和血管生成的抑制作用。此外,GBM患者的肿瘤样本显示miR-137和EZH2水平呈负相关。我们的结果表明,miR-137可能作为GBM的生物标志物,调节其活性可能代表一种治疗GBM患者的新策略。

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