Department of Joint Surgery, The Second Hospital of Shandong University, Jinan, 250033, Shandong, China.
School of Clinical Medicine, Qilu Medical University, Zibo, 255300, Shandong, China.
J Appl Genet. 2023 Sep;64(3):493-505. doi: 10.1007/s13353-023-00777-5. Epub 2023 Aug 5.
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.
A-to-I RNA 编辑是动物中一种普遍存在的 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，骨肉瘤是一种具有未知分子基础的复杂骨癌。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本中的 RNA 编辑组，并定量鉴定了骨肉瘤和正常样本之间可靠的差异编辑位点 (DES)。骨肉瘤中的 RNA 编辑效率显著增加，可能是由于编辑酶 ADAR1 和 ADAR2 的显著上调。骨肉瘤中上调的 DES 富集在 3'UTRs 中。引人注目的是，这些 3'UTR 位点进一步富集在基因 EMP2 和其他癌基因的 microRNA 结合区域，从而消除了对靶基因的 microRNA 抑制。相应地，这些促进肿瘤的基因在骨肉瘤中的表达升高。可能存在一条依赖 RNA 编辑的途径导致骨肉瘤。我们扩展了对 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未来预后和诊断具有重要价值。
