Genome-Wide Characterization of RNA Editing Sites in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis.

Javad Behroozi,Shirin Shahbazi,Habibollah Mahmoodzadeh,Mohammad Reza Bakhtiarizadeh,Mohamed Salem

doi:10.1155/2020/6493963

Abstract

RNA editing is a posttranscriptional 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 the ADAR family enzymes. Inosine is recognized by the biological machinery as guanosine; therefore, editing could have substantial functional effects throughout the genome. RNA editing could contribute to cancer either by 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 nontumor counterparts were retrieved from the GEO database. After preprocessing 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 the 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, and nearly half of them were located in 3′UTR. Our results revealed that 4868 editing sites were common in both normal and cancer tissues. From the remaining sites, 3985 and 3509 were exclusive to normal and cancer tissues, respectively. Further analysis revealed a 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 the diagnostic biomarkers and therapeutic targets in gastric cancer.

Highlights

RNA editing is a common and essential posttranscriptional alteration of RNA sequences, affecting millions of bases, expanding the transcriptome diversity and the functions of RNA transcripts [1]
The main obstacle in identifying bona fide RNA editing sites using RNA sequencing (RNA-seq) data is the distinction of RNA editing sites from rare SNPs and technical artifacts caused by sequencing or read mapping error
To accurately detect the RNA editing sites at the transcriptome-wide level in gastric cancer, we developed a computational approach by using a precise strategy

Summary

Introduction

RNA editing is a common and essential posttranscriptional alteration of RNA sequences, affecting millions of bases, expanding the transcriptome diversity and the functions of RNA transcripts [1]. Several types of RNA editing have been characterized, conversion of adenosine residues to inosine (A to I) is the most frequent type of editing in humans. This reaction is catalyzed by the double-stranded RNA- (dsRNA-) specific adenosine deaminase that acts on the RNA (ADAR) family [2, 3]. 3′UTRs usually comprise key elements and are involved in numerous regulatory processes. Editing in these elements can modulate the regulation of mRNA expression [3]. It is believed that editing of precursor microRNA may inhibit its processing to mature microRNA [7]

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Conclusion