Objective: RAN binding protein 17 (RANBP17) gene is a member of the nuclear transport receptor imoprtin family, and have a close relation to the tumorigenesis. However, the role and mechanism of RANBP17 in glioblastoma (GBM) remains unclear. Here, we comprehensively explored the expression, prognostic value, epigenetic modification, immune filtration, tumor stemness, tumor heterogeneity, upstream miRNA and biological function of RANBP17 in GBM combined bioinformatics analysis with functional experiments in vitro.
Methods: The expression of RANBP17 mRNA in GBM was analyzed by TIMER, UALCAN and CCGA databases. The prognostic value of RANBP17 was conducted by LinkedOmics, PrognoScan, and CGGA databases. Mutation status and type of RANBP17 was investigated by cBioportal database and COSMIC database, respectively. The RNA modification and DNA methylation of RANBP17 were analyzed by SangerBox and MethSurv databases. The relationships between RANBP17 expression and tumor heterogeneity, tumor stemness, and tumor immunity in human cancers were analyzed via the SangerBox, TISIDB and TIMER databases. Genes related to RANBP17 were screened by Linkedomics database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were analyzed by DAVID and STRING database, and the protein-protein interaction (PPI) network was constructed by Cytoscape software. Furthermore, miRWalk, ENCORI and miRDB database was used to predict upstream miRNA of RANBP17. Moreover, the counting kit 8 (CCK-8) assay, flow cytometry, and transwell assays were conducted to evaluate the impact of RANBP17 on the proliferation, apoptosis, migration and invasion in U251 cell.
Results: The expression of RANBP17 was downregulated and related to IDH mutation status, MGMT methylation status and 1p19q codeletion in GBM, which was associated with poor prognosis. RANBP17 was closely related to mRNA methylation genes, tumor heterogeneity and tumor stemness. GO and KEGG enrichment analysis indicated that RANBP17 was involved in neutrophil degranulation, response to estradiol and inflammatory response. Furthermore, the expression of RANBP17 was negatively correlated with B cell, CD4+ T cell, Macrophage, Neutrophil and dendritic cell, and positively correlated with tumor purity and CD8+ T cell. RANBP17 was also associated with hsa-miR-650, hsa-miR-361-5p, hsa-miR-421, hsa-miR-9-5p, hsa-miR-3612, hsa-miR-299-5p, hsa-miR-2115-3p and hsa-miR-19b-3p. Moreover, cell functional experiments in vitro demonstrated that overexpression of RANBP17 decreased cell proliferation, migration, invasion and facilitated apoptosis in GBM.
Conclusions: These findings revealed that RANBP17 was anticipated to be a promising prognostic and immunotherapeutic biomarker in GBM.