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Genome-Wide Characterization of RNA Editing Sites in Primary Gastric Adenocarcinoma through RNA-seq Data Analysis
International Journal of Genomics ( IF 2.9 ) Pub Date : 2020-12-18 , DOI: 10.1155/2020/6493963
Javad Behroozi 1 , Shirin Shahbazi 1 , Mohammad Reza Bakhtiarizadeh 2 , Habibollah Mahmoodzadeh 3
Affiliation  

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 3UTR. 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.

中文翻译:

通过RNA-seq数据分析对原发性胃腺癌中RNA编辑位点进行全基因组表征

RNA编辑是人类转录后的核苷酸修饰。在各种类型的RNA编辑中,腺苷到肌苷的替代在高级真核生物中最为普遍,这是由ADAR家族酶介导的。肌苷被生物机械识别为鸟苷;因此,编辑可能会对整个基因组产生实质性的功能影响。RNA编辑可通过独家编辑肿瘤抑制因子/促进基因或通过引入转录组多样性来促进癌症进展来促进癌症。在这里,我们提供了胃腺癌中RNA编辑位点的全面概述,并强调了它们对胃癌的可能贡献。从GEO数据库中检索到与8种胃腺癌及其配对的非肿瘤对应物对应的RNA-seq数据。在预处理和变体调用步骤之后,采用了严格的过滤管道来区分潜在的RNA编辑位点与SNP。对已识别的潜在编辑站点进行注释,并与DARNDED数据库中的站点进行比较。总共在所有样品中检测到12362个高可信度的腺苷至肌苷RNA编辑位点。其中,已知事件和新颖事件分别为12105和257。这些编辑位点在基因组区域分布不均,其中近一半位于3个 在所有样品中检测到12362个高可信度腺苷至肌苷RNA编辑位点。其中,已知事件和新颖事件分别为12105和257。这些编辑位点在基因组区域分布不均,其中近一半位于3个 在所有样品中检测到12362个高可信度腺苷至肌苷RNA编辑位点。其中,已知事件和新颖事件分别为12105和257。这些编辑位点在基因组区域分布不均,其中近一半位于3个UTR。我们的结果表明,在正常组织和癌组织中都共有4868个编辑位点。从其余部位来看,3985和3509分别是正常组织和癌组织所独有的。进一步的分析表明,这些位点之间存在大量差异编辑的事件,这些事件位于蛋白质编码基因和microRNA中。鉴于在胃腺癌和邻近正常组织中RNA编辑的独特模式,编辑后的位点有可能用作胃癌的诊断生物标志物和治疗靶标。
更新日期:2020-12-18
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