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

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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.