Abstract：
A-to-I RNA editing is a prevalent type of RNA modification in animals. The dysregulation of RNA editing has led to multiple human cancers. However, the role of RNA editing has never been studied in osteosarcoma, a complex bone cancer with unknown molecular basis. We retrieved the RNA-sequencing data from 24 primary osteosarcoma patients and 3 healthy controls. We systematically profiled the RNA editomes in these samples and quantitatively identified reliable differential editing sites (DES) between osteosarcoma and normal samples. RNA editing efficiency is dramatically increased in osteosarcoma, presumably due to the significant up-regulation of editing enzymes ADAR1 and ADAR2. Up-regulated DES in osteosarcoma are enriched in 3\'UTRs. Strikingly, such 3\'UTR sites are further enriched in microRNA binding regions of gene EMP2 and other oncogenes, abolishing the microRNA suppression on target genes. Accordingly, the expression of these tumor-promoting genes is elevated in osteosarcoma. There might be an RNA editing-dependent pathway leading to osteosarcoma. We expanded our knowledge on the potential roles of RNA editing in oncogenesis. Based on these molecular features, our work is valuable for future prognosis and diagnosis of osteosarcoma.
摘要：
A到IRNA编辑是动物中普遍存在的RNA修饰类型。RNA编辑的失调导致了多种人类癌症。然而,RNA编辑在骨肉瘤中的作用从未被研究过，一种分子基础未知的复杂骨癌.我们从24名原发性骨肉瘤患者和3名健康对照中检索了RNA测序数据。我们系统地分析了这些样品中的RNAeditome，并定量鉴定了骨肉瘤和正常样品之间的可靠差异编辑位点（DES）。RNA编辑效率在骨肉瘤中显著提高，可能是由于编辑酶ADAR1和ADAR2的显着上调。骨肉瘤中上调的DES在3'UTR中富集。引人注目的是，这样的3个UTR位点进一步富集在基因EMP2和其他癌基因的microRNA结合区中，取消对靶基因的microRNA抑制。因此，这些肿瘤促进基因的表达在骨肉瘤中升高。可能存在导致骨肉瘤的RNA编辑依赖性途径。我们扩展了我们对RNA编辑在肿瘤发生中的潜在作用的认识。基于这些分子特征，我们的工作对骨肉瘤的预后和诊断有价值.
