Abstract
Glioblastoma multiforme (GBM) is an aggressive primary brain tumor and one of the most lethal central nervous system tumors in adults. Despite significant breakthroughs in standard treatment, only about 5% of patients survive 5 years or longer. Therefore, much effort has been put into the search for identifying new glioma-associated genes. Tripartite motif-containing (TRIM) family proteins are essential regulators of carcinogenesis. TRIM8, a member of the TRIM superfamily, is abnormally expressed in high-grade gliomas and is associated with poor clinical prognosis in patients with glioma. Recent research has shown that TRIM8 is a molecule of duality (MoD) that can function as both an oncogene and a tumor suppressor gene, making it a "double-edged sword" in glioblastoma development. This characteristic is due to its role in selectively regulating three major cellular signaling pathways: the TP53/p53-mediated tumor suppression pathway, NFKB/NF-κB, and the JAK-STAT pathway essential for stem cell property support in glioma stem cells. In this review, TRIM8 is analyzed in detail in the context of GBM and its involvement in essential signaling and stem cell-related pathways. We also discuss the basic biological activities of TRIM8 in macroautophagy/autophagy, regulation of bipolar spindle formation and chromosomal stability, and regulation of chemoresistance, and as a trigger of inflammation.
Overview
- Focus of the study is to analyze the tripartite motif-containing (TRIM) family protein TRIM8 in the context of Glioblastoma multiforme (GBM) and its involvement in signaling and stem cell-related pathways.
- The study aims to identify the role of TRIM8 as both an oncogene and a tumor suppressor gene in GBM development and to understand its specific functions in selectively regulating three major cellular signaling pathways.
- The primary objective of the study is to provide a comprehensive review of the biological activities of TRIM8 in GBM, including its role in macroautophagy/autophagy, regulation of bipolar spindle formation and chromosomal stability, regulation of chemoresistance, and as a trigger of inflammation.
Comparative Analysis & Findings
- TRIM8 is abnormally expressed in high-grade gliomas and is associated with poor clinical prognosis in patients with glioma.
- TRIM8 functions as both an oncogene and a tumor suppressor gene in GBM development, making it a 'double-edged sword' in the disease.
- TRIM8 selectively regulates the TP53/p53-mediated tumor suppression pathway, NFKB/NF-κB, and the JAK-STAT pathway, which are essential for stem cell property support in glioma stem cells.
Implications and Future Directions
- The study highlights the significance of TRIM8 as a therapeutic target for GBM treatment, providing a potential new avenue for improving patient outcomes.
- Future research directions could include investigating the mechanisms by which TRIM8 regulates its target pathways and identifying potential therapeutic strategies for targeting TRIM8 in GBM.
- Understanding the dual role of TRIM8 in GBM development could lead to the development of more effective and personalized treatment strategies for patients with GBM.