Institute of Molecular Medicine, Sect. Molecular Cell Biology, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, 06120 Halle Saale, Germany.
Children's Cancer Institute Australia, Randwick, NSW 2031, Australia.
Int J Mol Sci. 2020 Jul 19;21(14):5098. doi: 10.3390/ijms21145098.
Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in -amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort ( = 498). Additionally, we found via Kaplan-Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs' potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.
神经母细胞瘤是一种常见的儿童癌症，近三分之一的患者仍会死亡，因此需要探索新的治疗策略。目前的实验治疗主要集中在抑制致癌转录因子信号。尽管 LIN28B、DICER 和其他 RNA 结合蛋白 (RBP) 在神经母细胞瘤的发展和患者预后中已有报道，但 RBP 在神经母细胞瘤中的作用相对较少研究。为了阐明参与扩增和其他高危神经母细胞瘤亚型的新 RBP，我们对一个大型原发性肿瘤队列（n = 498）中的 RBP 进行了差异 mRNA 表达分析。此外，我们通过 Kaplan-Meier 扫描分析发现，在 1483 个测试的 RBP 中，有 685 个具有神经母细胞瘤的预后价值。对于顶级推定致癌候选物，我们分析了它们在神经母细胞瘤细胞系中的表达，并总结了它们的特征和化学抑制剂的存在。此外，为了帮助解释它们与神经母细胞瘤亚型的关联，我们回顾了候选 RBP 作为生物标志物的潜力，以及它们在神经元和癌症背景下的机制作用。我们发现了几个高度显著的 RBP，包括 RPL22L1、RNASEH2A、PTRH2、MRPL11 和 AFF2，它们在神经母细胞瘤中尚未得到描述。尽管并非所有 RBP 都适合药物设计或具有预后意义，但我们表明，一些 RBP 具有强烈的抑制和机制研究的理由，代表了神经母细胞瘤治疗的另一种有前途的治疗策略。
