miR-340 suppresses glioblastoma multiforme.

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.

• Authors: Daquan Huang, Shuwei Qiu, Ruiguang Ge, Lei He, Mei Li, Yi Li, Ying Peng
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 11 Pg. 9257-70 (Apr 20 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25831237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BMI1 protein, human
• MIRN340 microRNA, human
• MicroRNAs
• X-Linked Inhibitor of Apoptosis Protein
• XIAP protein, human
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2
• Polycomb Repressive Complex 1
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• ROCK1 protein, human
• rho-Associated Kinases

Topics

• Apoptosis (genetics)
• Autophagy (genetics)
• Brain Neoplasms (genetics, mortality, pathology)
• Cell Cycle Checkpoints (genetics)
• Cell Differentiation (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Down-Regulation
• Enhancer of Zeste Homolog 2 Protein
• ErbB Receptors (metabolism)
• Gene Expression Regulation, Neoplastic
• Glioblastoma (genetics, mortality, pathology)
• Humans
• MicroRNAs (biosynthesis, genetics)
• Polycomb Repressive Complex 1 (metabolism)
• Polycomb Repressive Complex 2 (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• X-Linked Inhibitor of Apoptosis Protein (metabolism)
• rho-Associated Kinases (biosynthesis, genetics)