Lin Lvbiao, Zheng Yungui, Tu Yanyang, Wang Zhen, Liu Hui, Lu Xiaowen, Xu Liepeng, Yuan Jun
Department of Neurosurgery, First Affiliated Hospital of Medical College, Shantou University, Shantou 515041, China.
Department of Experimental Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
Hum Pathol. 2015 Jul;46(7):971-80. doi: 10.1016/j.humpath.2015.01.023. Epub 2015 Mar 18.
Our previous study demonstrated that enhancer of zeste homolog 2 (EZH2) overexpression may be associated with aggressive tumor progression and poor prognosis in human astrocytoma. The aim of this study was to investigate the underlying mechanisms of EZH2 on astrocytoma tumorigenesis. An online program miRWalk (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/) was used to predict possible microRNAs (miRNAs) that might target EZH2 messenger RNA (mRNA). Then the functions of the miRNA-EZH2 mRNA axis in astrocytoma cell proliferation, invasion, and migration were also assessed. We further evaluated the clinical value of the miRNA-EZH2 mRNA axis in astrocytomas. As a result, we identified EZH2 as a target gene of miR-144. In addition, forced expression of miR-144 suppressed astrocytoma cell proliferation, invasion, and migration by down-regulating EZH2. Moreover, miR-144 down-regulation and EZH2 mRNA up-regulation were both significantly associated with advanced World Health Organization grades and low Karnofsky performance status score of astrocytoma patients. Importantly, survival analysis identified the combined expression of miR-144 and EZH2 (miR-144/EZH2) as an independent prognostic factor for overall survival in astrocytoma patients. In conclusion, miR-144 may function as a tumor suppressor by regulating EZH2 expression, and miR-144/EZH2 expression may be a highly sensitive marker for the prognosis in astrocytoma patients.
我们之前的研究表明，zeste同源物2增强子（EZH2）的过表达可能与人星形细胞瘤侵袭性肿瘤进展及不良预后相关。本研究旨在探讨EZH2在星形细胞瘤发生中的潜在机制。使用在线程序miRWalk（http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/）预测可能靶向EZH2信使核糖核酸（mRNA）的微小核糖核酸（miRNA）。然后还评估了miRNA-EZH2 mRNA轴在星形细胞瘤细胞增殖、侵袭和迁移中的作用。我们进一步评估了miRNA-EZH2 mRNA轴在星形细胞瘤中的临床价值。结果，我们确定EZH2为miR-144的靶基因。此外，miR-144的强制表达通过下调EZH2抑制星形细胞瘤细胞的增殖、侵袭和迁移。此外，miR-144下调和EZH2 mRNA上调均与世界卫生组织高级别以及星形细胞瘤患者低卡诺夫斯基功能状态评分显著相关。重要的是，生存分析确定miR-144和EZH2的联合表达（miR-144/EZH2）为星形细胞瘤患者总生存的独立预后因素。总之，miR-144可能通过调节EZH2表达发挥肿瘤抑制作用，且miR-144/EZH2表达可能是星形细胞瘤患者预后的高度敏感标志物。
