Unveiling the Expression of UNC13C in Brain and Glioblastoma Cells

Objective: Glioblastoma (GBM) is the most aggressive type of brain tumor, accounting approximately half of malignant central nervous system tumors. Median overall survival remains below 15 months post-diagnosis. Current treatments include surgical resection, radiotherapy, and chemotherapy, primarily with temozolomide, yet the median overall survival remains below 15 months post-diagnosis. Understanding the molecular mechanisms of GBM is essential for developing novel therapeutic approaches. Among the implicated genes, the UNC13 protein family, particularly UNC13C, is of interest. While UNC13A and UNC13B have been linked to various neurological disorders, UNC13C has been less studied despite its involvement in neurotransmitter release and potential tumor-suppressive effects in other cancers. Our previous work indicated low expression levels of UNC13C in glioblastoma cell lines compared to healthy brain tissue, suggesting a role in GBM pathogenesis. In this study, we aimed to comprehensively evaluate UNC13C expression using web based bioinformatics tools and experimental approaches. Methods: We analyzed UNC13C expression across various tissues via Correlation Analyzer, confirming in glioblastoma tissues compared to healthy brain samples using the GEPIA and UALCAN databases. Additionally, we assessed UNC13C levels in glioblastoma cell lines (LN-18, A-172, U-87), human microglia (HMC3), and healthy astrocytes through quantitative real-time polymerase chain reaction (qRT-PCR). Results: Our findings reveal that UNC13C expression is notably reduced in glioblastoma cells, with the highest expression observed in healthy astrocytes, albeit at low levels. These results underscore the importance of UNC13C in GBM and highlight the need for further investigation into its role in tumor development and progression. Conclusion: This study provides the first report of UNC13C expression detailed in human cell lines both normal and glioblastoma, emphasizing its significance from a developmental perspective.