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Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from bronchial epithelial cell line induced by α-particles radiation

机译:全基因组识别和分析α粒子辐射诱导的从支气管上皮细胞系恶性转化的细胞系中A至I RNA编辑事件

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摘要

Adenosine (A) to inosine (I) RNA editing is the most prevalent RNA editing mechanism in humans and plays critical roles in tumorigenesis. However, the effects of radiation on RNA editing were poorly understood, and a deeper understanding of the radiation-induced cancer is imperative. Here, we analyzed BEP2D (a human bronchial epithelial cell line) and radiation-induced malignantly transformed cell lines with next generation sequencing. By performing an integrated analysis of A-to-I RNA editing, we found that single-nucleotide variants (SNVs) might induce the downregulation of ADAR2 enzymes, and further caused the abnormal occurrence of RNA editing in malignantly transformed cell lines. These editing events were significantly enriched in differentially expressed genes between normal cell line and malignantly transformed cell lines. In addition, oncogenes CTNNB1 and FN1 were highly edited and significantly overexpressed in malignantly transformed cell lines, thus may be responsible for the lung cancer progression. Our work provides a systematic analysis of RNA editing from cell lines derived from human bronchial epithelial cells with high-throughput RNA sequencing and DNA sequencing. Moreover, these results provide further evidence for RNA editing as an important tumorigenesis mechanism.
机译:腺苷(A)到肌苷(I)RNA编辑是人类中最流行的RNA编辑机制,并且在肿瘤发生中起关键作用。但是,人们对辐射对RNA编辑的影响了解甚少,因此必须对辐射诱发的癌症有更深入的了解。在这里,我们用下一代测序技术分析了BEP2D(人支气管上皮细胞系)和辐射诱导的恶性转化细胞系。通过对A-to-I RNA编辑进行综合分析,我们发现单核苷酸变异(SNV)可能会诱导ADAR2酶的下调,并进一步在恶性转化的细胞系中引起RNA编辑的异常发生。这些编辑事件在正常细胞系和恶性转化细胞系之间的差异表达基因中显着丰富。此外,癌基因CTNNB1和FN1在恶性转化的细胞系中被高度编辑并显着过表达,因此可能与肺癌的进展有关。我们的工作通过高通量RNA测序和DNA测序,对来源于人支气管上皮细胞的细胞系的RNA编辑进行系统分析。而且,这些结果为RNA编辑作为重要的肿瘤发生机制提供了进一步的证据。

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