Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
Department of Neurosurgery, Tehran University of Medical Science, Tehran, Iran.
Cell Mol Biol Lett. 2023 Jan 23;28(1):6. doi: 10.1186/s11658-023-00418-z.
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.
胶质母细胞瘤（GBM）是一种侵袭性原发性脑肿瘤，也是成人中枢神经系统肿瘤中最致命的肿瘤之一。尽管在标准治疗方面取得了重大突破，但只有约 5%的患者能够存活 5 年或更长时间。因此，人们一直在努力寻找新的与神经胶质瘤相关的基因。三结构域蛋白（TRIM）家族蛋白是癌症发生的重要调节因子。TRIM8 是 TRIM 超家族的成员，在高级别神经胶质瘤中异常表达，并与神经胶质瘤患者的不良临床预后相关。最近的研究表明，TRIM8 是一种双重功能分子（MoD），可以作为癌基因和抑癌基因发挥作用，使其成为神经胶质瘤发展中的“双刃剑”。这种特性是由于其在选择性调节三个主要细胞信号通路中的作用：TP53/p53 介导的肿瘤抑制途径、NFKB/NF-κB 和 JAK-STAT 途径，这些途径对于神经胶质瘤干细胞的干性维持至关重要。在这篇综述中，我们详细分析了 TRIM8 在 GBM 中的作用及其在关键信号通路和干细胞相关通路中的参与。我们还讨论了 TRIM8 在巨自噬/自噬、双极纺锤体形成和染色体稳定性调节以及化疗耐药性调节中的基本生物学活性，以及作为炎症触发因素的作用。
