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

Zahra Razaghi Bahabadi, Mohammad Saeed Kahrizi, Hamed Hosseinalizadeh, Daniel J Klionsky, Omid Mohamadzadeh, Hamed Mirzei

Journal: Cellular & molecular biology letters 2023;28(1):6

PMID: 36690946

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.

© 2023. The Author(s).

Address: Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.; Department of Neurosurgery, Tehran University of Medical Science, Tehran, Iran.; Department of Surgery, Alborz University of Medical Sciences, Karaj, Alborz, Iran.; School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.; Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran.; Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.; Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran. [email protected].
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