Journal
ONCOTARGET
Volume 6, Issue 11, Pages 9257-9270Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3288
Keywords
glioblastoma multiforme; miR-340; ROCK1; biomarker
Categories
Funding
- National Natural Science Foundation of China [81272197, 81402065]
- Culture program for Key project of National Natural Science Foundation of China of Sun Yat-Sen University [10ykjc26]
- International Collaboration Program of Universities in Guangdong province [2012gjhz001]
- Science & Technique Plan fund of Guangdong Province [2013B021800098]
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University [KLB09001]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]
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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.
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