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miR-340 suppresses glioblastoma multiforme
Daquan Huang1,2, Shuwei Qiu1, Ruiguang Ge3
1Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
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.
Insights
MicroRNA-340 (miR-340) is downregulated in glioblastoma multiforme (GBM). Restoring miR-340 inhibits glioma growth, induces cell death, and may serve as a prognostic biomarker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) deregulation is implicated in cancer development.
- miR-340 is frequently downregulated across various cancer types.
- The specific role of miR-340 in glioblastoma multiforme (GBM) is not well understood.
Purpose of the Study:
- To investigate the biological function and clinical significance of miR-340 in glioblastoma.
- To identify the molecular mechanisms underlying miR-340's effects in glioma.
Main Methods:
- Analysis of miR-340 expression in glioma cell lines and patient tissues.
- In vitro functional assays to assess proliferation, cell cycle, apoptosis, motility, autophagy, and differentiation.
- Western blotting and luciferase reporter assays to identify and validate miR-340 targets.
- ROCK1 silencing experiments.
Main Results:
- miR-340 expression was significantly downregulated in glioma tissues and cell lines.
- Lower miR-340 levels correlated with reduced patient survival.
- Restoration of miR-340 suppressed glioma cell proliferation, induced cell-cycle arrest and apoptosis, reduced motility, and promoted autophagy and differentiation.
- miR-340 targeted and suppressed oncogenes including AKT, EZH2, EGFR, BMI1, XIAP, and ROCK1.
- ROCK1 was identified as a direct functional target, and its silencing mimicked miR-340's anti-tumor effects.
Conclusions:
- miR-340 functions as a tumor suppressor in glioblastoma.
- miR-340 plays a critical role in inhibiting glioma cell proliferation, survival, and metastasis.
- miR-340 represents a potential prognostic biomarker and therapeutic target for GBM.
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