基于二代测序数据研究神经母细胞瘤中的RNA编辑现象

发布时间：2019-04-03 21:13

【摘要】：近年来,越来越多的研究指出RNA编辑作为一种转录后修饰行为,通过改变编码区域和非编码区域的序列,不仅增加了蛋白质的多样性,而且在转录后的调控过程中也扮演着非常重要的作用。RNA编辑事件被多次报道与癌症有关,例如乳腺癌、前列腺癌等,目前关于神经母细胞瘤中RNA编辑事件的研究还比较少。本文通过提出一个只利用RNA测序数据检测RNA编辑事件的分析流程,通过验证得出本文的分析流程具有很高的准确率,并利用这个分析流程分析了497个神经母细胞瘤样本中的RNA编辑事件。通过分析,总共发现645,603个RNA编辑事件,但是不同样本之间的重合度非常低。通过分析不同期神经母细胞瘤样本中发生的RNA编辑事件,发现每一期疾病样本中独有的RNA编辑事件所占的比例非常高；分析不同诊断年龄神经母细胞瘤样本中的RNA编辑事件,结果表明诊断年龄接近的样本组之间的RNA编辑事件的重合度更高；通过分析高危组和中低危组样本中RNA编辑事件的编辑度,揭示了大多数RNA编辑事件的编辑度在高危组病人中显著地低于中低危组病人,并且这些RNA编辑事件所处的基因中有些已经被报道过与神经母细胞瘤密切相关,例如NTRK1, CHD5和DNAJC11;通过分析RNA编辑事件与OS d和EFS_d之间的关联性,得出所有样本共同发生的RNA编辑事件的编辑度与OS d和EFS_d没有显著的相关性；最后,分析了外显子区域发生的RNA编辑事件,结果显示病情较好的样本组中发生的非同义突变RNA编辑事件的个数反而更多。本文的研究结果表明,大多数RNA编辑事件对于人体的健康发展是有利的,这些RNA编辑事件不发生或者RNA编辑事件编辑度降低可能会导致神经母细胞瘤病情的恶化。
[Abstract]:In recent years, more and more studies have pointed out that as a kind of post-transcriptional modification behavior, RNA editing not only increases the diversity of proteins by changing the sequences of coding and non-coding regions, but also increases the diversity of proteins. RNA editing events have been reported to be related to cancer, such as breast cancer, prostate cancer, and so on. At present, there are few studies on RNA editing events in neuroblastoma. In this paper, we propose an analysis flow only using RNA sequencing data to detect RNA editing events, and verify that the analysis process of this paper has a very high accuracy. The RNA editing events in 497 neuroblastoma samples were analyzed by this analysis process. Through analysis, a total of 645603 RNA editing events were found, but the coincidence between the different samples was very low. By analyzing the RNA editing events in different neuroblastoma samples, it was found that the percentage of unique RNA editing events in each phase of the disease sample was very high. The RNA editing events in neuroblastoma samples of different diagnostic ages were analyzed. The results showed that the coincident degree of RNA editing events was higher among the groups with similar diagnostic age. By analyzing the editing degree of RNA editing events in high-risk group and middle-low risk group, it is revealed that the editing degree of most RNA editing events in high-risk group is significantly lower than that in middle-and low-risk group. And some of the genes where these RNA editing events are located have been reported to be closely related to neuroblastoma, such as NTRK1, CHD5 and DNAJC11;. By analyzing the relationship between RNA editing events and OS d and EFS_d, it is concluded that the editing degree of RNA editing events co-occurring in all samples has no significant correlation with OS d and EFS_d. Finally, the RNA editing events occurred in exons were analyzed, and the results showed that the number of non-synonymous mutation RNA editing events in the group with better condition was more than that in the control group. The results of this study show that most of the RNA editing events are beneficial to the healthy development of human body. The non-occurrence of these RNA editing events or the decrease of editing degree of RNA editing events may lead to the deterioration of neuroblastoma.
【学位授予单位】：华东师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41

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