Comprehensive Characterization of RNA Editing in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis

Abstract

RNA editing is a post-transcriptional nucleotide modification in humans. Of the various types of RNA editing, the adenosine to inosine substitution is the most widespread in higher eukaryotes, which is mediated by ADAR family enzyme. Inosine is recognized by the biological machineries as guanosine, therefore, editing can potentially rendering substantial functional effects throughout the genome, depending on where it located. RNA editing could contribute to cancer by either exclusive editing of tumor suppressor/promoting genes or by introducing transcriptomic diversity to promote cancer progression. Here, we provided a comprehensive overview of the RNA editing sites in gastric adenocarcinoma and highlighted some of their possible contributions to gastric cancer. RNA-seq data corresponding to 8 gastric adenocarcinoma and their paired non-tumor counterparts were retrieved from GEO database. After pre-possessing and variant calling steps, a stringent filtering pipeline was employed to distinguish potential RNA editing sites from SNPs. The identified potential editing sites were annotated and compared with those in DARNED database. Totally, 12362 high-confidence adenosine to inosine RNA editing sites were detected across all samples. Of these, 12105 and 257 were known and novel editing events, respectively. These editing sites were unevenly distributed across genomic regions, nearly half of them were located in 3´UTR. Indeed, 4868, 3985 and 3509 editing sites were found to be common in both tissue, normal specific and cancer specific, respectively. Further analysis revealed significant number of differentially edited events among these sites, which were located in protein coding genes and microRNAs. Given the distinct pattern of RNA editing in gastric adenocarcinoma and adjacent normal tissue, edited sites have the potential to serve as biomarkers and therapeutic targets in gastric cancer diagnose, management and treatment.