TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt

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. GRAPHICAL ABSTRACT: [Image: see text]