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

利用公共基因组和转录组数据揭示癌症-RNA 编辑关系

基本信息

批准号：
10643949
负责人：
Xinshu Grace Xiao
金额：
$ 38.22万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10643949
关键词：
3&apos Untranslated Regions ADAR1 Address Adenosine Affect Amino Acid Sequence Base Sequence Bioinformatics Cancer Control Cancer Patient Cells Code Collection Complement DNA Sequence Alteration DRADA2b protein Data Data Set Double-Stranded RNA Enzymes Epithelium Future Gene Expression Genes Genomics Goals Heterogeneity Human Immune Response Genes Immune response Immunotherapy Inosine Interferon Activation Interferons Label Malignant Neoplasms Mammals Mesenchymal Cell Neoplasm Methodology Methods Modification Molecular Mutation Natural Immunity Nucleotides Organism Outcome Pathway interactions Patients Pattern Phenotype Proteins Proteomics RNA RNA Editing RNA Sequences RNA analysis RNA-Binding Proteins Regulation Reporting Research Role Sampling Site Structure Technology Transcript Untranslated RNA Validation Work cancer cell cancer risk cancer type cell type genetic architecture human disease immunoregulation insertion/deletion mutation insight mRNA Stability neuropsychiatric disorder novel posttranscriptional prevent response secondary analysis success transcriptome transcriptome sequencing transcriptomics treatment response tumor

项目摘要

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.

项目概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编辑是一种流行的RNA类型修饰，即通过插入、删除或替换来改变 RNA 序列核苷酸。在哺乳动物中，最常见的 RNA 编辑类型是腺苷至肌苷（A-to-I）编辑。在 ADAR 酶的催化下，A 到 I 编辑是最常见的 RNA 类型人类编辑，发生在大多数人类转录本中。在过去的几十年里，伟大在了解少数 A 到 I 编辑位点的关键功能方面取得了进展癌症相关基因，其中大部分改变蛋白质编码序列。由于最近 RNA 测序 (RNA-seq) 技术和生物信息学方法的进步，各种生物体中数量空前的 A 到 I 编辑位点已被编目。重要的是，许多癌症类型中都报道了广泛的异常 RNA 编辑。此外，越来越多的证据支持 ADAR 和 RNA 编辑水平与患者的生存率或对治疗的反应。然而，仍然存在许多问题，其中最重要的其中包括 ADAR 和 RNA 编辑的不清楚机制癌症相关通路和异常 RNA 背后的未知调控机制癌症编辑。在这个项目中，我们建议扩展我们最近在开发和在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，辅以进一步的生物信息预测和实验验证，以预测和验证RNA编辑的分子功能和相关调控机制。这部作品将使人们对 RNA 编辑的分子基础有了前所未有的了解并为 RNA 编辑参与人类癌症提供新的见解。