Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Center for RNA Biology, The Ohio State University, Columbus, OH 43210, USA.
Genes (Basel). 2024 Jul 1;15(7):864. doi: 10.3390/genes15070864.
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.
癌症是一种复杂且异质性的疾病，其中许多遗传和表观遗传变化发生在肿瘤的发生和进展过程中。最近的研究表明，RNA 水平的变化也参与了肿瘤发生，如腺苷到肌苷（A-to-I）RNA 编辑。在这里，我们系统地研究了大量非霍奇金淋巴瘤（NHL）样本中的全转录组 A-to-I 编辑事件。使用一种计算管道，该管道确定了在已知 A-to-I 编辑位点处 NHL 和正常样本之间编辑水平的显著差异，我们鉴定出 NHL 亚型和正常样本之间存在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域，许多这样的位点显示基因表达水平和编辑效率之间存在很强的相关性，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有直接影响。此外，我们通过证明 NHL 和正常样本甚至 NHL 亚型可以仅基于全基因组 RNA 编辑谱来区分，建立了 RNA 编辑与 NHL 之间的强联系。我们的研究在 NHL 中建立了 RNA 编辑、癌症和异常基因调控之间的强联系。
