| Objective: Frizzled-7(FZD7),a Wnt signaling receptor,was evolutionary conserved gene and participated in the growth and development of organisms,such as neural crest induction,gastrulation,regulation of digestive system development and intestinal homeostasis.In recent years,it has emerged as a critical regulator in the proliferation,migration,invasion,epithelial-mesenchymal transition and apoptosis of several types of cancer.However,the definite function by which FZD7 promotes glioma progression remains unclear.Therefore,the aim of this study was to assess the prognostic influence of FZD7 up-regulation in patients with glioma,as well as its effects on malignant properties and the underlying mechanism.Methods: FZD7 expression was compared between glioma and normal brain tissues using public databases,the relationship between FZD7 expression level and glioma grade was also studied and confirmed using clinical samples.Functional annotation of FZD7 was conducted with bioinformatics methods,and its influence on survival was assessed using survival curve and COX proportional hazard regression.Next,the specific roles of FZD7 in glioma cell malignant behavior were evaluated with FZD7-overexpressed or-knockdown cell lines.The effects of FZD7 on the proliferation of glioma cells were studied by CCK-8,colony formation assay and tumorigenicity analysis in vivo.The effects of FZD7 on the migration and invasion of glioma cells were studied by scratch-wound assay and cell invasion assay.The influence of FZD7 on epithelial-mesenchymal transition(EMT)and WNT signaling-related markers were further assessed.Finally,combined with the basic experimental results and database information,we analyzed the relationship between FZD7 and glioblastoma subtypes and its significance in clinical application.Results: Compared with normal brain tissue,FZD7 expression was upregulated in glioblastoma,and its overexpression significantly correlated with glioma grade.Patients with high FZD7 expression have lower overall survival rate.FZD7 was an independent risk factor in the multivariate analysis.Through GO,GSEA and GSVA algorithms,we found that FZD7 may affects glioma cells' proliferation,migration,cell adhension and EMT.Subsequently,FZD7 knockdown significantly inhibited glioma cell proliferation,migration,invasion and EMT were confirmed through cytological experiments.After FZD7 knockdown,the phosphorylation level of GSK3 b and the b-catenin expression level both decreased in glioma cells.In addition,we also found that mesenchymal subtype cells have higher levels of FZD7 than other subtypes and FZD7 can function as a marker of mesenchymal subtype and EMT in glioma.Last,we analyzed several studies about FZD7 and post-operative therapy resistance,and confirmed FZD7 low-expression patients had a survival advantage compared to FZD7 high-expression patients who receiving chemotherapy or radiotherapy.Conclusion: FZD7 may promote the proliferation,migration,invasion and EMT of glioma,highlighting its potential as a novel prognostic marker and promising therapeutic target. |
PDF Full Text Request