REMR：鉴定RNA编辑介导的miRNA调节癌症
REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers
影响因子:4.10000
分区:生物学3区 / 生化与分子生物学3区
发表日期:2024 Dec
作者:
Xu Zhou, Haizhou Liu, Fei Hou, Zong-Qing Zheng, Xinyu Cao, Quan Wang, Wei Jiang
摘要
腺苷对肌苷（A-TO-I）RNA编辑的失调与癌症进展有关。但是，考虑到缺乏有效的鉴定方法，对A-TO-I RNA编辑如何纳入miRNA调节以调节癌症的基因表达的全面了解仍然不清楚。为此，我们介绍了一种名为REMR的信息理论算法，以系统地识别12,006个A-TO-I RNA介导的miRNA调节三重态（RNA编辑位点，miRNA和基因），基于十种主要癌症类型，基于来自Cancerame Genome Atlas（TCGA）的多组学分析数据。通过分析功能富集，转录调节网络和蛋白质 - 蛋白质相互作用（PPI）网络，我们表明RNA编辑介导的miRNA调节潜在地影响了关键的癌症相关功能，例如凋亡，细胞周期，耐药性和免疫力。此外，三胞胎可以用作具有不同预后或药物反应的癌症亚型分类的生物标志物，从而强调了这种调节的临床相关性。此外，还构建了在线资源（http://www.jianglab.cn/remr/），以支持我们发现的便利检索。总而言之，我们的研究系统地剖析了RNA编辑介导的miRNA法规，从而提供了一种宝贵的资源，以理解RNA编辑作为癌症的表相关调节剂的机制。
Abstract
Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.