MicroRNA-105 Targets SOX9 And Inhibits Human Glioma Cell Progression

Glioma is the most common primary brain tumor and accounts for nearly 46 percent of all adult brain tumors.Nearly 350,000 people are diagnosed with glioma every year.Despite recent advances in treatment,the median survival of glioblastoma multiforme(GBM)patients is only approximately 15 months.New biological molecular targets and strategies are urgently needed for the treatment of gliomas.MicroRNAs(miRNAs)are small non-coding RNAs.It has been reported that miRNAs play vital roles in the regulation of important processes,including developmental regulation,organ formation,cell proliferation and apoptosis.Recent studies have shown that the abnormal expression of miRNAs in tumor has become one of the hot spots in tumor diagnosis and treatment.Among these functional miRNAs,miR-105 is significantly dysregulated in many human cancers and acts as a tumor suppressor or an oncogene.In addition,the expression of miR-105 was substantially down-regulated in glioma tissues,and patients with low miR-105 expression had significantly poorer survival.However,the role of miR-105 in genesis and development of glioma is still unclear.In this study,we used Quantitative RT-PCR analysis,luciferase reporter assay and CCK-8 assay,flow cytometry and transwell cell cultures,aimed to determine the expression of miR-105 in glioma tissues and cell lines,and measure the effects of miR-105 on glioma cell proliferation,apoptosis and invasion,and determine the direct target gene of miR-105,and then explore the potential mechanism of miR-105 together.These results may provide atheoretical basis for the subsequent application in the treatment of glioma.Our results as following:1)The expression of miR-105 was significantly down-regulated in glioma tissues and cell lines.2)miR-105 up-regulation repressed the proliferation and invasion,and induced apoptosis in glioma cells.3)Luciferase reporter assay results showed that SOX9 was a direct target of miR-105.SOX9 expression was significantly increased and inversely correlated with miR-105 expression in glioma tissues.4)SOX9 down-regulation suppressed the proliferation and invasion,and induced apoptosis in glioma cells.5)SOX9 up-regulation rescued the inhibition of cell proliferation and invasion,and the increase in cell apoptosis caused by miR-105 up-regulation in glioma cells.6)SOX9 down-regulation inhibited the expression of SOX9,TCF4,c-MYC,cyclin D1 and AXIN2 protein in glioma cells.TCF4 up-regulation restored the expression of SOX9,TCF4,c-MYC,cyclin D1 and AXIN2 protein in glioma cells pretreated with SOX9 down-regulation vectors.TCF4 up-regulation reversed the suppression of proliferation and invasion,and the increase in apoptosis caused by SOX9 down-regulation.7)miR-105 over-expression inhibited the expression of SOX9,TCF4,c-MYC,cyclin D1 and AXIN2 protein in glioma cells.SOX9 up-regulation restored the expression of SOX9,TCF4,c-MYC,cyclin D1 and AXIN2 protein in glioma cells pretreated with miR-105 vectors.TCF4 up-regulation restored the expression of SOX9,TCF4,c-MYC,cyclin D1 and AXIN2 protein in glioma cells pretreated with miR-105 vectors.TCF4 up-regulation rescued the inhibition of cell proliferation and invasion,and the increase in cell apoptosis caused by miR-105 up-regulation in glioma cells.In summary,our results showed that miR-105 was significantly down-regulated in glioma tissues and glioma cell lines.We also showed that miR-105 inhibited glioma cell proliferation and invasion,and promoted apoptosis by directly targeting SOX9/TCF4 signaling.