Regulation Of Glioma Cells Migration By DYRK2

Objective1.To investigate the expression level of Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2(DYRK2)in glioma tissues,and analyze the relationship between DYRK2 expression and some clinicopathological parameters.2.To study the possible role of DYRK2 in glioma cells migration,and explore the possible mechanism involved in glioma cells migration regulated by DYRK2.Methods1.Western blot(WB)was employed to study the expression of DYRK2 in normal brain tissues and different glioma tissues.Immunohistochemistry(IHC)was performed to detect the expression of DYRK2 and E-cadherin on 84 paraffin-embedded glioma clinical slices.The correlation between DYRK2 expression and the clinicopathological features of the patients was analyzed,including age,gender,tumor location,surgy and WHO grade.Kaplan–Meier curve analysis were used to evaluate the influence of DYRK2 expression on the prognosis of patients with glioma.2.WB was employed to detect the expression of DYRK2 in several glioma cells,U87 and H4 glioma cells were selected for the study.In U87 cells,overexpressed DYRK2 and detecte the expression level of E-cadherin,Vimentin and Snail;in H4 cells,interfering the expression of DYRK2 and then analyze the expression of E-cadherin,Vimentin and Snail by WB.3.Wound-healing and transwell assays were performed to explore the migration of glioma cells.In addition,WB was used to detect the proteins expression of related signal pathway to further investigate the possible mechanism involved in glioma cells migration regulated by DYRK2.Results1.Western blot showed that the expression of DYRK2 in normal brain tissues was considerably higher than that in glioma tissues.And the expression of DYRK2 was diminished gradually from Grade II to Grade IV.2.IHC data revealed that the expression of DYRK2 deceased when the malignant degree increased while the expression of E-cadherin having the same tendency.Moreover,DYRK2 expression was apparently associated with WHO grades(P<0.05),while there was no correlation with other prognostic factors such as patient's gender,age,tumor location,extent of resection or tumor size.Pearson's analysis confirmed a positive correlation between DYRK2 and E-cadherin expression(r=0.616,P<0.01).Kaplan–Meier survival curves indicated that down-regulation of DYRK2 was apparently associated with poor overall survival.3.In glioma cells,WB showed that the expression level of E-cadherin was in consistent with DYRK2 while Vimentin and Snail expression was opposite to DYRK2.4.Overexpressing DYRK2 could inhibit the migration of U87 glioma cells;silencing the expression of DYRK2 would promote the migration of H4 glioma cells.5.WB revealed that overexpressed DYRK2 could inhibit the expression of PI3 K,p-AKT and p-GSK3? in U87 cells;interfering the expression of DYRK2 could induce PI3 K,p-AKT and p-GSK3? expression in H4 cells.Conclusions1.DYRK2 exhibited lower expression in glioma tissues and its expression was associated with WHO grades statistically;and the xpression of DYRK2 was related to poor prognosis of glioma patients,suggesting that DYRK2 may play an important role in the progress of glioma.2.DYRK2 could regulate the migration of glioma cells by PI3K/AKT/GSK3? pathway,suggesting that DYRK2 might be a potential target for glioma treatment.