Zhou Xu, Liu Haizhou, Hou Fei, Zheng Zong-Qing, Cao Xinyu, Wang Quan, Jiang Wei
Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.
Fujian Provincial Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Comput Struct Biotechnol J. 2024 Sep 18;23:3418-3429. doi: 10.1016/j.csbj.2024.09.011. eCollection 2024 Dec.
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.
腺苷到次黄苷（A到I）的RNA编辑失调与癌症进展有关。然而，鉴于缺乏有效的识别方法，目前尚不清楚A到I的RNA编辑如何整合到miRNA调控中以调节癌症中的基因表达。为此，我们引入了一种基于信息论的算法REMR，基于来自癌症基因组图谱（TCGA）的多组学分析数据，系统地识别了十种主要癌症类型中的12,006个A到I RNA编辑介导的miRNA调控三联体（RNA编辑位点、miRNA和基因）。通过功能富集分析、转录调控网络分析和蛋白质-蛋白质相互作用（PPI）网络分析，我们发现RNA编辑介导的miRNA调控可能影响关键的癌症相关功能，如细胞凋亡、细胞周期、耐药性和免疫。此外，三联体可作为生物标志物，用于对具有不同预后或药物反应的癌症亚型进行分类，突出了这种调控的临床相关性。此外，我们还构建了一个在线资源（http://www.jianglab.cn/REMR/），以方便检索我们的研究结果。总之，我们的研究系统地剖析了RNA编辑介导的miRNA调控，从而为理解RNA编辑作为癌症中一种表观转录组调节剂的机制提供了宝贵的资源。
