Genomic Identification of RNA Editing Through Integrating Omics Datasets and the Clinical Relevance in Hepatocellular Carcinoma
Genomic Identification of RNA Editing Through Integrating Omics Datasets and the Clinical Relevance in Hepatocellular Carcinoma
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通过整合组学数据集进行 RNA 编辑的基因组鉴定及其在肝细胞癌中的临床相关性
DOI：
10.3389/fonc.2020.00037
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发表时间：
2020-02-14
影响因子：
4.7
通讯作者：
Bai, Zhenyu
中科院分区：
文献类型：
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作者：
Chen, Juan;Wang, Lu;Bai, Zhenyu
RNA编辑是一种广泛的转录后机制，在人类癌症中引入单核苷酸变化的RNA。在这里，我们描述了来自癌症基因组图谱(TCGA)的373例肝细胞癌(HCC)和50例邻近正常肝脏样本的全球RNA编辑谱，发现大多数编辑事件往往发生在中等编辑度(20%-30%)的少数样本中。此外，这些RNA编辑更倾向于蛋白质编码基因的A-to-I RNA编辑，特别是在3‘非编码区。考虑到DNA突变与RNA编辑的相关性，我们的分析发现，RNA编辑可能是肝细胞癌患者肝癌危险基因DNA突变的一种互补事件。我们接下来确定了454个与肝癌相关的编辑位点，其中许多位于相同的基因上，具有相同的编辑模式。编辑的功能结果揭示了2,086个功能编辑位点，并表明大多数编码区的编辑是非同义变体。此外，我们的结果表明，在3‘非编码区的编辑往往会影响miRNA与靶的结合，并且编辑程度似乎与基因表达呈负相关。最后，我们发现46个带有结果的肝癌相关编辑站点能够区分肝癌患者的预后差异，这表明它们具有临床相关性。总之，我们的结果强调了RNA编辑是研究肝癌机制和临床治疗的宝贵分子资源。
RNA editing is a widespread post-transcriptional mechanism to introduce single nucleotide changes to RNA in human cancers. Here, we characterized the global RNA editing profiles of 373 hepatocellular carcinoma (HCC) and 50 adjacent normal liver samples from The Cancer Genome Atlas (TCGA) and revealed that most editing events tend to occur in minor percentage of samples with moderate editing degrees (20–30%). Moreover, these RNA editing prefer to be A-to-I RNA editing in protein coding genes, especially in 3′UTR regions. Considering the association between DNA mutation and RNA editing, our analysis found that RNA editing maybe a complementary event for DNA mutation of HCC risk genes in HCC patients. We next identified 454 HCC-related editing sites, and many locate on the same genes with the same editing patterns. The functional consequences of editing revealed 2,086 functional editing sites and demonstrated that most editing in coding regions are non-synonymous variations. Furthermore, our results showed that editing in the 3′UTR regions tend to influence miRNA–target binding, and the editing degree seems to be negatively correlated with gene expression. Finally, we found that 46 HCC-related editing sites with consequence are able to distinguish the prognosis differences of HCC patients, suggesting their clinical relevance. Together, our results highlight RNA editing as a valuable molecular resource for investigating HCC mechanisms and clinical treatments.