RNA binding protein-mediated post-transcriptional gene regulation in medulloblastoma.
RNA binding protein-mediated post-transcriptional gene regulation in medulloblastoma.
复制标题
RNA结合蛋白介导的髓母细胞瘤转录后基因调控。
DOI：
10.14348/molcells.2014.0008
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发表时间：
2014-05
影响因子：
3.8
通讯作者：
Vogel C
中科院分区：
文献类型：
--
作者：
Bish R;Vogel C
髓母细胞瘤是儿童中最常见的恶性脑肿瘤，其机制现在开始通过对患者肿瘤的体细胞突变、mRNA表达模式和表观遗传特征的高通量研究来揭示。对大量髓母细胞瘤患者的肿瘤基因组进行测序的研究中出现的一个主题是RNA结合蛋白的频繁突变。结合多个RNA靶标的蛋白质可以在转录后水平上作为基因表达的主调节剂，以协调细胞过程并改变细胞的表型。RNA结合蛋白靶基因的鉴定可能会凸显成髓细胞瘤发生的重要途径，而这些途径无法单独通过转录组学研究来检测。此外，RNA结合蛋白的子集是有吸引力的药物靶标。例如，由于其抑制RNA解旋酶的能力而正在开发作为抗病毒靶标的化合物也可以通过靶向关键RNA结合蛋白在成神经管细胞瘤治疗的新方法中进行测试。在这篇综述中，我们讨论了一些RNA结合蛋白，包括Musashi 1（MSI 1），DEAD（Asp-Glu-Ala-Asp）盒解旋酶3X-连锁（DDX 3X），DDX 31和细胞分裂周期和凋亡调节因子1（CCAR 1），它们在髓母细胞瘤的生长和/或维持中起着潜在的关键作用。
Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.