ABSTRACT
CDCA3, a cell cycle regulator gene that plays a catalytic role in many tumors, was initially identified as a regulator of cell cycle progression, specifically facilitating the transition from the G2 phase to mitosis. However, its role in glioma remains unknown. In this study, bioinformatics analyses (TCGA, CGGA, Rembrandt) shed light on the upregulation and prognostic value of CDCA3 in gliomas. It can also be included in a column chart as a parameter predicting 3- and 5-year survival risk (C index = 0.86). According to Gene Set Enrichment Analysis and gene ontology analysis, the biological processes of CDCA3 are mainly concentrated in the biological activities related to cell cycle such as DNA replication and nuclear division. CDCA3 is closely associated with many classic glioma biomarkers (CDK4, CDK6), and inhibitors of CDK4 and CDK6 have been shown to be effective in tumor therapy. We have demonstrated that high expression of CDCA3 indicates a higher malignancy and poorer prognosis in gliomas.
Subject(s)
Biomarkers, Tumor , Brain Neoplasms , Cell Cycle Proteins , Glioma , Molecular Targeted Therapy , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Computational Biology , Glioma/genetics , Glioma/metabolism , Molecular Targeted Therapy/methods , Prognosis , Up-RegulationABSTRACT
Human cytomegalovirus (HCMV) is associated with epithelial-mesenchymal transition (EMT) in glioma cells; however, its underlying action mechanism remain ambiguous. In this study, we investigated the effects of receptor-interacting protein 2 (RIP2) and nuclear factor (NF)-κB on EMT in HCMV-infected glioma LN-18 cells. Wound healing and invasion assays were used to evaluate the migration and invasion of cells. Western blotting and immunofluorescence microscopy were used to determine the protein expression levels. We found that HCMV induced enhanced migration and invasion of LN-18 cells, activation of the RIP2/NF-κB signaling pathway, downregulation of epithelial cell marker (E-cadherin) expression, and upregulation of mesenchymal cell marker (N-cadherin and vimentin) expression. Moreover, inhibition of RIP2 or NF-κB inhibited the induction of HCMV in LN-18 cells. Therefore, HCMV induces EMT in glioma cells by promoting the activation of NF-κB signaling pathway via the upregulation of RIP2 expression.
Subject(s)
Cytomegalovirus , NF-kappa B , Humans , Cadherins/metabolism , Cell Line, Tumor , Cell Movement , Cytomegalovirus/metabolism , Epithelial-Mesenchymal Transition , NF-kappa B/metabolism , Up-RegulationABSTRACT
BACKGROUND: The age of glioma plays a unique role in prognosis. We hypothesized that age is not positively correlated with survival prognosis and explored its exact relationship. METHODS: Glioma was identified from the SEER database (between 2000 and 2018). A multivariate Cox proportional regression model and restricted cubic spline (RCS) plot were used to assess the relationship between age and prognosis. RESULTS: A total of 66465 patients with glioma were included. Hazard ratios (HR) for ten-year by age: 0-9 years, HR 1.06 (0.93-1.20); 10-19 years: reference; 20-29 years, HR 0.90 (0.82-1.00); 30-39 years, HR 1.14 (1.04-1.25); 40-49 years, HR 2.09 (1.91-2.28); 50-59 years, HR 3.48 (3.19-3.79); 60-69 years, HR 4.91 (4.51-5.35);70-79 years, HR 7.95 (7.29-8.66); 80-84 years, HR 12.85 (11.74-14.06). After adjusting for covariates, the prognosis was not positively correlated with age. The smooth curve of RCS revealed this non-linear relationship: HR increased to 10 years first, decreased to 23 years, reached its lowest point, and became J-shaped. CONCLUSION: The relationship between age and glioma prognosis is non-linear. These results challenge the applicability of current age groupings for gliomas and advocate the consideration of individualized treatment guided by precise age.
