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.
[1]Jilin Univ, Coll Basic Med Sci, Key Lab Pathobiol, Minist Educ, 126 Xinmin St, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Univ, Hosp 2, Eye Ctr, Changchun 130021, Jilin, Peoples R China.
[3]Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130021, Jilin, Peoples R China.
[4]Jilin Univ, Hosp 1, Res Ctr Neurosci, Changchun 130021, Jilin, Peoples R China.
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