Huang Daquan, Qiu Shuwei, Ge Ruiguang, He Lei, Li Mei, Li Yi, Peng Ying
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.
Oncotarget. 2015 Apr 20;6(11):9257-70. doi: 10.18632/oncotarget.3288.
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.
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。
