miR-340 suppresses glioblastoma multiforme

// Daquan Huang 1, 2 * , Shuwei Qiu 1 * , Ruiguang Ge 3 , Lei He 1 , Mei Li 1 , Yi Li 1 , Ying Peng 1, 2 1 Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China 2 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China 3 Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-Sen University, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Ying Peng, e-mail: docpengy123@163.com Keywords: glioblastoma multiforme, miR-340, ROCK1, biomarker Received: January 07, 2015      Accepted: February 07, 2015      Published: March 16, 2015 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.