OncoTargets and Therapy (Jul 2019)
microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway
Abstract
Jianwu Jia,1,* Jing Wang,1,* Meifeng Yin,1 Yongdong Liu21Department of Neurosurgery, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, People’s Republic of China; 2Department of Pediatrics, Weifang People’s Hospital, Weifang, Shandong 261041, People’s Republic of China*These authors contributed equally to this workBackground: Aberrant microRNA (miRNA) expression has been widely reported to play a crucial role in the progression and development of glioblastoma (GBM). miR-605 has been identified as a tumor-suppressing miRNA in several types of human cancers. Nevertheless, the expression profile and detailed roles of miR-605 in GBM remain unclear and need to be further elucidated.Materials and methods: RT-qPCR analysis was utilized for the determination of miR-605 expression in GBM tissues and cell lines. In addition, CCK-8 assay, transwell migration and invasion assays, as well as sub-cutaneous xenograft mouse models were utilized to evaluate the effects of miR-605 upregulation in GBM cells. Notably, the potential mechanisms underlying the activity of miR-605 in the malignant phenotypes of GBM were explored.Results: We observed that expression of miR-605 was reduced in GBM tissues and cell lines. Decreased miR-605 expression exhibited significant correlation with KPS score. The overall survival rate in GBM patients with low miR-605 expression was lower than that of patients with high miR-605 expression. Increased miR-605 expression suppressed the proliferation, migration, and invasion of U251 and T98 cells. In addition, miR-605 upregulation impaired tumor growth in vivo. Furthermore, SRY-Box 9 (SOX9) was identified as a direct target gene of miR-605 in U251 and T98 cells. SOX9 expression was shown to exhibit an inverse correlation with miR-605 expression in GBM tissues. Moreover, silencing of SOX9 expression mimicked the tumor-suppressing roles of miR-605 in U251 and T98 cells, while SOX9 restoration rescued the suppressive effects of miR-605 overexpression in the same. Notably, miR-605 suppressed the PI3K/Akt pathway in GBM in vitro and in vivo.Conclusion: These results demonstrated that miR-605 acts as a tumor suppressor in the development of GBM by directly targeting SOX9 and inhibiting the activation of the PI3K/Akt pathway, suggesting its potential role as a therapeutic target for GBM.Keywords: glioblastoma multiforme, microRNA-605, malignant phenotypes, SRY-Box 9
