Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Cells. 2022 Apr 5;11(7):1231. doi: 10.3390/cells11071231.
RNA editing alters the nucleotide sequence and has been associated with cancer progression. However, little is known about its prognostic and regulatory roles in glioma, one of the most common types of primary brain tumors. We characterized and analyzed RNA editomes of glioblastoma and isocitrate dehydrogenase mutated (IDH-MUT) gliomas from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas (CGGA). We showed that editing change during glioma progression was another layer of molecular alterations and that editing profiles predicted the prognosis of glioblastoma and IDH-MUT gliomas in a sex-dependent manner. Hyper-editing was associated with poor survival in females but better survival in males. Moreover, noncoding editing events impacted mRNA abundance of the host genes. Genes associated with inflammatory response (e.g., , a key mediator of innate immunity) and fatty acid oxidation (e.g., , the rate-limiting enzyme in fatty acid β-oxidation) were editing-regulated and associated with glioma progression. The above findings were further validated in CGGA samples. Establishment of the prognostic and regulatory roles of RNA editing in glioma holds promise for developing editing-based therapeutic strategies against glioma progression. Furthermore, sexual dimorphism at the epitranscriptional level highlights the importance of developing sex-specific treatments for glioma.
RNA 编辑改变了核苷酸序列，并与癌症进展有关。然而，人们对其在神经胶质瘤（最常见的原发性脑肿瘤之一）中的预后和调控作用知之甚少。我们对来自癌症基因组图谱 (TCGA) 和中国脑胶质瘤基因组图谱 (CGGA) 的胶质母细胞瘤和异柠檬酸脱氢酶突变型 (IDH-MUT) 神经胶质瘤的 RNA 编辑组进行了表征和分析。我们表明，胶质瘤进展过程中的编辑变化是分子改变的另一个层面，并且编辑谱以性别依赖的方式预测胶质母细胞瘤和 IDH-MUT 神经胶质瘤的预后。高编辑与女性的生存不良相关，但与男性的生存改善相关。此外，非编码编辑事件影响宿主基因的 mRNA 丰度。与炎症反应相关的基因（例如，一种先天免疫的关键介质）和脂肪酸氧化相关的基因（例如，脂肪酸β-氧化的限速酶）受到编辑调控，并与胶质瘤的进展相关。上述发现进一步在 CGGA 样本中得到了验证。在胶质瘤中建立 RNA 编辑的预后和调控作用有望为开发针对胶质瘤进展的编辑治疗策略提供依据。此外，转录后水平的性别二态性突出了为胶质瘤开发特异性别治疗的重要性。
