Sun Jie, Zheng Guodong, Gu Zhengtao, Guo Zhenhui
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.
J Neurooncol. 2015 May;122(3):481-9. doi: 10.1007/s11060-015-1753-x. Epub 2015 May 5.
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.
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。