MIR-608 inhibits the migration and invasion of glioma stem cells by targeting macrophage migration inhibitory factor

Abstract

Glioma stem cells (GSCs) contribute to the malignant biological behavior of these tumors and have also been shown to be resistant to radiation and chemotherapy. Recently, a variety of microRNAs (miRNAs) has been found to present altered expression and to play an important oncogenic role or tumor-suppressive function in cancer stem cells (CSCs). microRNA-608 (miR-608) is one of the newly discovered microRNAs, and its biological functions remain unclear. Human macrophage migration inhibitory factor (MIF) is a well known oncogene associated with tumor recurrence and the poor prognosis of gliomas. In the present study, we found that MIR-608 negatively regulated the gene expression of MIF at the post-transcriptional level and plays a tumor-suppressive role by targeting MIF in GSCs. We found that MIR-608 expression was significantly downregulated and the expression levels of the MIF gene and protein showed an increase in the GSCs. MIR-608 overexpression significantly attenuated the proliferation, migration and invasion, and induced the apoptosis of GSCs. The dual-luciferase reporter system revealed that the 3'UTR of MIF is a direct target of MIR-608, and MIR-608 negatively regulates the gene expression of MIF at the posttranscriptional level by targeting its 3'UTR. Furthermore, we demonstrated that MIR-608 overexpression inhibited the malignant behavior of GSCs by downregulating MIF. Western blot results showed that the inhibition of MIF resulted in the inactivation of the PI3K/AKT and JNK pathways. These results demonstrate that MIR-608 acts as a potential tumor suppressor and provide insight into new therapeutic targets for malignant glioma.