Abstract
MicroRNA-124 (miR-124) has been shown to be downregulated in glioma; however, its biological functions in glioma are not yet fully understood. The aim of this study was to examine the Smad4‑dependent effects of miR‑124 on C6 glioma cell proliferation. In this study, the level of miR‑124 was found to be enhanced in C6 cells upon transfection with miR‑124 mimics, and the mechanisms of action of miR‑124 in C6 cells were investigated by reverse transcriptase-quantitative polymerase chain reaction, MTT assay, western blot analysis and luciferase reporter assays in vitro. The results revealed that miR‑124 expression was significantly lower in the C6 cells than in either normal rat brain tissue or astrocytes. Upon the overexpression of miR‑124, the proliferation of the C6 cells decreased and Smad4 expression was significantly suppressed. Smad4 was identified as a direct target of miR‑124 through luciferase reporter assays. Furthermore, miR‑124 was found to modulate signal transducer and activator of transcription 3 (Stat3) by downregulating Smad4 expression. Using small interfering RNA targeting Smad4 mRNA, we also confirmed that miR‑124 downregulated c‑Myc by modulating Smad4 expression. In addition, caspase‑3 expression was induced by miR‑124 overexpression, but not via Smad4 downregulation. On the whole, our results demonstrate that miR‑124 upregulation inhibits the growth of C6 glioma cells by targeting Smad4 directly. These findings may be clinically useful for the development of therapeutic strategies directed toward miR‑124 function in patients with glioma.