Xiaobin Huang

Glioblastoma (GBM) is the most common and lethal brain tumor with limited therapeutic strategies and incomplete studies on its progression and mechanisms. This study aims to reveal potential prognostic marker genes associated with GBM cell invasion, and establish an effective prognostic model for GBM patients. Differentially expressed genes (DEGs) were screened from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), differentially invasive-related genes was obtained, qRT-PCR was used to verify gene expression. The risk scores of individual patients, univariate and multivariate Cox regression were analyzed to investigate the correlation between risk values and glioblastoma, Finally, the risk scores with the prognostic clinical characteristics of the patients, such as PFS, OS were used to build a comprehensive GBM prognostic model. Five DEGs (GZMB, COL22A1, MSTN, CRYGN and OSMR) were significantly associated with GBM prognosis. Pseudotemporal analysis, risk scores (PFS, OS) based on tumor cells revealed that prognostic genes were associated with tumor proliferation and progression. The final prognostic model was developed and validated with good performance with higher accuracy(C-index: 0.675), and it was found that the risk value can serve as an independent prognostic factor for patients with glioblastoma (p < 0.05). We constructed a comprehensive prognostic model related to invasion in GBM patients using genetic profiles, survival curves, immune infiltration, and radiotherapy face susceptibility. The model has good predictive ability.

Glioblastoma is a malignant CNS tumor with an extremely poor prognosis. F-box protein 11 (FBXO11) has E3 ubiquitin ligase activity and participates in the pathogenesis of multiple tumors but the role and mechanism of FBXO11 activity in glioblastoma remain unknown. In this study, FBXO11 was first observed to be downregulated in glioblastoma tissues and cell lines. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) and colony formation assays and enzyme linked immunosorbent assay (ELISA) demonstrated that overexpression of FBXO11 suppressed proliferation and aerobic glycolysis and induced cell cycle arrest in U251-MG and A172 cells. FBXO1 decreased cell division cycle 25 A (Cdc25A) expression through ubiquitin degradation in a coprecipitation assay. A Western blot assay validated FBXO11 suppression of PKM2 dephosphorylation and c-Myc-mediated aerobic glycolysis via reduction of Cdc25A. In addition, a rescue experiment revealed that FBXO11 suppressed proliferation and aerobic glycolysis, both of which were reversed by overexpression of Cdc25A. FBXO11 overexpression also inhibited tumorigenesis via suppressing Cdc25A expression in vivo. These findings indicate that FBXO11 suppresses cell proliferation and aerobic glycolysis in glioblastomas by mediating the ubiquitin degradation of Cdc25A thereby providing insight into mechanisms of glioblastoma tumorigenesis and identifying a new potential therapeutic strategy.

Background: Non-SMC condensin I complex subunit G (NCAPG) is expressed in various human cancers, including gliomas. However, its biological function in glioma remains unclear. The present study was designed to determine the biological functions of NCAPG in glioma and to evaluate the association of NCAPG expression with glioma progression.Methods: Clinical data on patients with glioma were obtained from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), the Gene Expression Omnibus (GEO), and the Rembrandt and Gravendeel databases. The correlations among NCAPG expression, pathological characteristics, and clinical outcome were evaluated. In addition, the correlations of NCAPG expression with immune cell infiltration and glioma progression were analyzed.Results: NCAPG expression was higher in gliomas than in adjacent normal tissues. Higher expression of NCAPG in gliomas correlated with poorer prognosis, unfavorable histological features, absence of mutations in the isocitrate dehydrogenase gene (IDH), absence of chromosome 1p and 19q deletions, and responses to chemoradiotherapy. Univariate and multivariate Cox analysis demonstrated, in addition to patient age, tumor grade, absence of IDH mutations, and absence of chromosome 1p and 19q deletions, NCAPG expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. In addition, high expression of NCAPG correlated with tumor infiltration of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. Gene set enrichment analysis (GSEA) indicated that high NCAPG expression was associated with cell proliferation and immune response-related signaling pathways. NCAPG knockdown in glioma cell lines significantly reduced cell survival, proliferation, and migration.Conclusion: NCAPG expression correlates with glioma progression and immune cell infiltration, suggesting that NCAPG expression may be a useful prognostic biomarker for glioma.