REMR：RNA编辑介导的miRNA调控在癌症中的识别

REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers

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Computational and Structural Biotechnology Journal

影响因子:4.1

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

DOI: 10.1016/j.csbj.2024.09.011

摘要

腺苷到肌苷（A-to-I）RNA编辑的失调已被认为与癌症进展有关。然而，关于A-to-I RNA编辑如何嵌入miRNA调控以调节癌症中的基因表达的机制尚不完全清楚，原因是缺乏有效的识别方法。为此，我们提出了一种基于信息论的算法REMR，系统性识别了10个主要癌症类型中通过多组学数据（来自癌症基因组图谱，TCGA）分析的12,006个A-to-I RNA编辑介导的miRNA调控三元组（RNA编辑位点、miRNA和靶基因）。通过功能富集、转录调控网络和蛋白质-蛋白质相互作用（PPI）网络分析，发现RNA编辑介导的miRNA调控可能影响关键的癌症相关功能，如凋亡、细胞周期、药物抗性和免疫反应。这些调控三元组还能作为生物标志物，用于区分具有不同预后或药物反应的癌症亚型，展示其临床意义。此外，我们建立了一个在线资源（http://www.jianglab.cn/REMR/），方便检索研究结果。综上所述，本研究系统性解析了RNA编辑介导的miRNA调控，提供了理解RNA编辑作为表转录组调节因子在癌症中作用机制的重要资源。

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.