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微小RNA-340抑制多形性胶质母细胞瘤。

miR-340 suppresses glioblastoma multiforme.

作者信息

Huang Daquan, Qiu Shuwei, Ge Ruiguang, He Lei, Li Mei, Li Yi, Peng Ying

机构信息

Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Oncotarget. 2015 Apr 20;6(11):9257-70. doi: 10.18632/oncotarget.3288.

Abstract

Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM.

摘要

微小RNA(miR)失调促进肿瘤发生。在多种癌症中均观察到miR - 340表达下调。然而,miR - 340在多形性胶质母细胞瘤(GBM)中的生物学功能仍 largely未知。在本研究中,我们证明miR - 340在胶质瘤细胞系和组织中表达均下调。与低表达miR - 340的患者相比,高表达miR - 340的GBM患者生存期显著延长。生物学功能实验表明,miR - 340的恢复显著抑制胶质瘤细胞增殖,诱导细胞周期停滞和凋亡,抑制细胞迁移并促进自噬和终末分化。机制研究表明,miR - 340过表达抑制了包括p - AKT、EZH2、EGFR、BMI1和XIAP在内的多个癌基因。此外,ROCK1被验证为miR - 340的直接功能靶点,沉默ROCK1模拟了mR - 340的抗肿瘤作用。我们的研究结果表明miR - 340作为胶质瘤杀手的重要作用,并提示其可能作为GBM的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b6/4496215/6b957a738933/oncotarget-06-9257-g001.jpg

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