Abstract
Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-β1 (TGF-β1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-β. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-β-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-β1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.
Highlights
Glioblastoma is the most common and aggressive primary brain tumor and represent 12-15% of intracranial tumours and 60-75% of astrocytic tumours [1, 2]
The expression of epidermal growth factor receptor (EGFR) and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues
The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors
Summary
Glioblastoma is the most common and aggressive primary brain tumor and represent 12-15% of intracranial tumours and 60-75% of astrocytic tumours [1, 2]. Malignant gliomas account for approximately 70% of new cases of malignant primary brain tumors diagnosed in adults [3, 4]. It has been demonstrated that aberrant miRNAs expression correlates with various human cancers and indicates that miRNAs can function as oncogenes or tumor suppressor genes [16,17,18,19]. These findings suggest the miRNAs may play an important role in the pathogenesis of glioblastoma. Our data indicate the roles of miR-564 in the control of cell growth and invasion in glioblastoma, and suggest the potential therapeutic application of miR-564 for glioblastoma patients
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