Target Regulation Of CypB/ CD147 By MiR-206 And Its Clinical Significance In Gliomas

Background: Gliomas are the most common and malignant brain tumors,accounting for 45-55% of all intracranial tumors.Glioma is the most aggressive primary tumor,which is invasive growth and difficult to completely removed by surgery,is the main prognostic factors of glioma patient.miR-206 is a newly discovered conserved small non-coding RNA that regulates gene expression by targeting multiple molecules.Abnormal expression of miR-206 is closely related to the tumor occurrence and development.The role of miR-206 in the pathogenesis of glioma is still need to be investigated.Objective:Analysis of miR-206 in gliomas were differentially expressed,to determine CypB is miR-206 downstream target gene.Investigate the expression levels of miR-206 and CypB、CD147 mRNA and protein in human glioma.Moreover,investigate the relationship between miR-206 and CypB,CD147,and evaluate the expression of miR-206 in the regulation of the development of gliomas and assess the value of miR-206 in predicting the prognosis of gliomas.Method: Fifty cases of patients with gliomas via pathological confirmation were collected in past 3 years.10 cases of normal brain tissue by cortex fistulization from brain tumor resection were taken as control group.1.The target miRNAs were screened by GEO data and their target genes in gliomas were identified by sites such as Targetscan and the target gene receptors were included in the study2.The expression of target miRNAs,target gene and target gene receptors mRNA was quantified by quantitative Real-time PCR assays.3.Western Blot and immunohistochemical staining were used to detect the expression of CypB and CD147 protein.4.To investigate the correlation between expression level of target miRNAs and the clinicopathological features of glioma patients.5.Kaplan-Meier survival curve was used to analyze the correlation between the expression of target miRNAs and the overall survival and progression-free survival.The prognosis of patients with glioma was analyzed by Cox proportional hazards regression model.6.Data were analyzed using SPSS 21 and GraphPad Prism software.The correlation between target miRNAs,target gene and target gene receptors expression levels and tumor grade were analyzed,and the correlation between target miRNAs,target gene and target gene receptors expression were analyzed as well.Results: 1.The target miRNA was miR-206 by GEO data and CypB was the target gene by Targets and miRanda can website.2.The expression level of miR-206 in glioma tissues was significantly lower than that in normal brain tissues(P <0.001);The expression of miR-206 in high grade gliomas was lower than that in low grade gliomas.3.In addition,the low expression of miR-206 in glioma tissue was significantly correlated with tumor size(P = 0.019),tumor grade(P = 0.009)and KPS(P = 0.019).4.Kaplan-Meier survival analysis showed that patients with low expression of miR-206 had shorter progression-free survival(PFS)and overall survival(OS)than those with higher expression of miR-206.In addition,univariate and multivariate analysis showed that miR-206 expression levels were independent prognostic factors for OS and PFS.5.CypB,CD147 mRNA,and the relative expression level of protein in grade Ⅱ,Ⅲ,Ⅳ gliomas were statistically significant(P <0.05);Immunohistochemical staining showed that the higher the expression of CypB and CD147 protein,the higher of glioma grade,the difference was statistically significant(P <0.05).6.The expression of miR-206 was negatively correlated with the expression of CypB and CD147 mRNA.Conclusion: Low miR-206 expression is associated with poor overall survival in patients with glioma.miR-206 regulates the development and progression of glioma through CypB / CD147.Therefore,miR-206 could be a potential valuable marker in glioma progression.