Exploiting public genomic and transcriptomic data to uncover cancer-RNA editing relationships

项目摘要 该项目旨在更好地了解RNA编辑在癌症中的调控和功能 通过分析现有的组学数据集。RNA编辑是一种普遍的RNA类型 修饰，其中RNA序列通过插入、缺失或取代 个核苷酸在哺乳动物中，最常见的RNA编辑类型是腺苷到肌苷（A到I） 编辑.在阿达尔酶的催化下，A-to-I编辑是最普遍的RNA类型 编辑在人类中，发生在大多数人类转录本中。在过去的几十年里， 在理解少数A-to-I编辑站点的关键功能方面取得了进展， 癌症相关基因，其中大多数改变蛋白质编码序列。由于最近 RNA测序技术和生物信息学方法的进展， 已经为各种生物体编目了前所未有数量的A到I编辑位点。 重要的是，在许多癌症类型中已经报道了广泛的异常RNA编辑。 此外，越来越多的证据支持阿达尔和RNA编辑水平与 患者生存率或对治疗的反应。然而，许多问题仍然存在，最重要的是， 其中包括阿达尔和RNA编辑的机制尚不清楚， 癌症相关通路和异常RNA的未知调控机制 在癌症中编辑。在这个项目中，我们建议扩大我们最近的成功， 在RNA编辑研究中应用生物信息学方法来应对上述挑战。我们 将利用来自不同类型癌症的大量RNA-seq数据集， 样品我们将开发和应用新的方法来充分利用这些数据集， 通过进一步的生物信息学预测和实验验证， 验证RNA编辑的分子功能和相关调控机制。这项工作 将使人们对RNA编辑的分子基础有一个前所未有的了解 并为RNA编辑参与人类癌症提供新的见解。

Project Summary This project aims to better understand the regulation and function of RNA editing in cancer through analysis of existing omics data sets. RNA editing is a prevalent type of RNA modification where the RNA sequences are altered through insertion, deletion or substitution of nucleotides. In mammals, the most common type of RNA editing is adenosine to inosine (A-to-I) editing. Catalyzed by the ADAR enzymes, A-to-I editing is the most prevalent type of RNA editing in human, occurring in the majority of human transcripts. In the past few decades, great progress was made to understand the critical function of a small number of A-to-I editing sites in cancer-related genes, most of which alter protein-coding sequences. Owing to the recent advances in RNA-sequencing (RNA-seq) technologies and bioinformatic methodologies, an unprecedented number of A-to-I editing sites have been cataloged for various organisms. Importantly, widespread aberrant RNA editing has been reported in a number of cancer types. In addition, increasing evidence supports that ADAR and RNA editing levels are associated with patient survival or response to therapy. However, many questions remain, the most significant ones including the unclear mechanisms through which ADAR and RNA editing contribute to cancer-related pathways and the unknown regulatory mechanisms underlying aberrant RNA editing in cancer. In this project, we propose to extend our recent successes at developing and applying bioinformatic approaches in RNA editing studies to address the above challenges. We will capitalize on the large collection of RNA-seq data sets derived from different types of cancer samples. We will develop and apply novel methodologies to make full use of these data sets, complemented by further bioinformatic prediction and experimental validations, to predict and validate the molecular function of RNA editing and related regulatory mechanisms. This work will allow a previously unattained level of understanding of the molecular basis of RNA editing and provide new insights to the involvement of RNA editing in human cancer.