PDF(Pubmed)
Abstract：
Cancer is a complex and heterogeneous disease, in which a number of genetic and epigenetic changes occur in tumor onset and progression. Recent studies indicate that changes at the RNA level are also involved in tumorigenesis, such as adenosine-to-inosine (A-to-I) RNA editing. Here, we systematically investigate transcriptome-wide A-to-I editing events in a large number of samples from Non-Hodgkin lymphomas (NHLs). Using a computational pipeline that determines significant differences in editing level between NHL and normal samples at known A-to-I editing sites, we identify a number of differentially edited editing sites between NHL subtypes and normal samples. Most of the differentially edited sites are located in non-coding regions, and many such sites show a strong correlation between gene expression level and editing efficiency, indicating that RNA editing might have direct consequences for the cancer cell\'s aberrant gene regulation status in these cases. Moreover, we establish a strong link between RNA editing and NHL by demonstrating that NHL and normal samples and even NHL subtypes can be distinguished based on genome-wide RNA editing profiles alone. Our study establishes a strong link between RNA editing, cancer and aberrant gene regulation in NHL.
摘要：
癌症是一种复杂的异质性疾病,其中许多遗传和表观遗传变化发生在肿瘤的发病和进展。最近的研究表明，RNA水平的变化也与肿瘤发生有关。例如腺苷到肌苷(A-to-I)RNA编辑。这里,我们系统地研究了大量非霍奇金淋巴瘤(NHL)样本中转录组范围的A-to-I编辑事件.使用计算管道确定NHL和正常样本在已知的A-to-I编辑位点的编辑水平的显著差异，我们在NHL亚型和正常样本之间鉴定了许多差异编辑的编辑位点.大多数差异编辑的位点位于非编码区，许多这样的位点在基因表达水平和编辑效率之间显示出很强的相关性，这表明在这些情况下，RNA编辑可能对癌细胞的异常基因调控状态产生直接影响。此外，我们通过证明仅基于全基因组RNA编辑谱就可以区分NHL和正常样品，甚至NHL亚型，从而在RNA编辑和NHL之间建立了牢固的联系。我们的研究建立了RNA编辑之间的紧密联系，NHL中的癌症和异常基因调控。
