Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Biomolecules. 2024 Jul 6;14(7):803. doi: 10.3390/biom14070803.
Medulloblastoma is the most common pediatric brain cancer, with about five cases per million in the pediatric population. Current treatment strategies have a 5-year survival rate of 70% or more but frequently lead to long-term neurocognitive defects, and recurrence is relatively high. Genomic sequencing of medulloblastoma patients has shown that , which encodes an RNA helicase involved in the process of translation initiation, is among the most commonly mutated genes in medulloblastoma. The identified mutations are 42 single-point amino acid substitutions and are mostly not complete loss-of-function mutations. The pathological mechanism of mutations in the causation of medulloblastoma is poorly understood, but several studies have examined their role in promoting cancer progression. This review first discusses the known roles of DDX3X and its yeast ortholog Ded1 in translation initiation, cellular stress responses, viral replication, innate immunity, inflammatory programmed cell death, Wnt signaling, and brain development. It then examines our current understanding of the oncogenic mechanism of the mutations in medulloblastoma, including the effect of these mutations on growth, biochemical functions, translation, and stress responses. Further research on DDX3X's mechanism and targets is required to therapeutically target DDX3X and/or its downstream effects in medulloblastoma progression.
髓母细胞瘤是最常见的儿童脑癌，儿童人群中每百万例中有约 5 例。目前的治疗策略的 5 年生存率达到 70%或更高，但常常导致长期神经认知缺陷，且复发率相对较高。对髓母细胞瘤患者的基因组测序表明，DDX3X 是最常发生突变的基因之一，它编码一种 RNA 解旋酶，参与翻译起始过程。鉴定出的突变是 42 个单点氨基酸取代，大多数不是完全丧失功能的突变。突变在髓母细胞瘤发病机制中的病理机制尚不清楚，但已有几项研究探讨了其在促进癌症进展中的作用。这篇综述首先讨论了 DDX3X 及其酵母直系同源物 Ded1 在翻译起始、细胞应激反应、病毒复制、先天免疫、炎症程序性细胞死亡、Wnt 信号传导和大脑发育中的已知作用。然后，本文检查了我们目前对髓母细胞瘤中 突变的致癌机制的理解，包括这些 突变对生长、生化功能、翻译和应激反应的影响。需要进一步研究 DDX3X 的机制和靶点，以在髓母细胞瘤进展中靶向 DDX3X 及其下游效应进行治疗。
