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TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt
Hamed Hosseinalizadeh1, Omid Mohamadzadeh2, Mohammad Saeed Kahrizi3
1Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
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.
Insights
Tripartite motif-containing protein 8 (TRIM8) acts as a double-edged sword in glioblastoma, functioning as both an oncogene and tumor suppressor. Its dual role impacts key signaling pathways and offers potential therapeutic targets for this aggressive brain tumor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma multiforme (GBM) is a lethal brain tumor with poor prognosis.
- Identifying novel glioma-associated genes is crucial for developing new treatments.
- Tripartite motif-containing (TRIM) proteins are implicated in carcinogenesis.
Approach:
- This review analyzes the dual role of TRIM8 in glioblastoma.
- It details TRIM8's involvement in TP53/p53, NFKB/NF-κB, and JAK-STAT signaling pathways.
- The review also discusses TRIM8's functions in autophagy, spindle formation, chromosomal stability, chemoresistance, and inflammation.
Key Points:
- TRIM8 exhibits dual functionality, acting as both an oncogene and a tumor suppressor in GBM.
- Its expression is linked to poor clinical prognosis in glioma patients.
- TRIM8 selectively regulates critical cellular pathways, including tumor suppression and stem cell properties.
Conclusions:
- TRIM8's complex role as a molecule of duality (MoD) makes it a significant factor in glioblastoma development.
- Understanding TRIM8's functions in various cellular processes is vital for targeting GBM.
- TRIM8 represents a potential therapeutic target for glioblastoma.
