title: 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 post-transcriptional 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.
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; C000591804:MIRN608 microRNA, human; D008263:Macrophage Migration-Inhibitory Factors; D035683:MicroRNAs; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human