对抗癌药物作用产生应答的vlinc类的长链非编码RNA的鉴定

发布时间：2018-04-22 02:28

本文选题：vlincRNAs + K562　；参考：《华侨大学》2017年硕士论文

【摘要】：大多数人类基因组(98%)不编码蛋白质,但是大部分的DNA序列(约75%)能够转录为非编码RNA(Non-coding RNA,ncRNA)。并且,近年来的研究发现,长链非编码RNA(Long Non-Coding RNA,lncRNA,指转录长度大于200kb的非编码RNA)在高等生物的许多重要生物过程中发挥作用。它们通常通过与多种功能性基因的相互调控来发挥作用,同时,它们的异常可造成癌症等多种疾病的形成。其中,极长基因间非编码RNA(Very Long Integenic Non-Coding RNAs,vlincRNAs)为一类特殊的长链非编码RNA,目前的研究结果已经显现了其参与到早期胚胎发育以及癌症发生的过程中,但仍有潜在功能未被证实。vlincRNAs为癌症发生的早期阶段的研究提供了一个新方向。考虑到大量未被发现的lnc-和vlincRNAs以及它们在细胞各项生理活动中的作用,这些转录物或许掌握着一个细胞发育或癌变的关键。并且,越来越多的研究表明,lncRNAs在抗癌药物的作用过程中发挥着重要作用。因此,这些转录产物可能与很多抗癌药物作用的分子机制相关。本论文通过研究抗癌药物对vlincRNAs表达的影响,从而了解vlincRNAs的功能。具体地说,我们利用单分子测序平台,对使用多种抗癌药物处理后的人类白血病细胞K562进行RNA测序,对测序结果进行分析,筛选vlincRNAs。本文特别关注两种抗癌药物——伊马替尼(Gleevec)和司美替尼。其中,伊马替尼是一种公认的治疗作用较好且销量很高的抗癌药物,司美替尼是一个仍处于实验阶段的抗癌药物。我发现经过这两种药物处理K562细胞系之后,一些vlincRNAs的表达发生了显著的变化。另外,我通过多次重复实验以及多种实验手段已经确定了KVUG1、KVUG2和KVUG3这3条vlincRNAs可能参与到了伊马替尼所调控的细胞增殖、新陈代谢和细胞免疫过程中。
[Abstract]:Most human genomes do not encode proteins, but most of the DNA sequences can be transcribed into non-coding RNA(Non-coding RNAs. Moreover, in recent years, it has been found that long chain noncoding RNA(Long Non-Coding (LNNRNAs), which refer to non-coding RNAs whose transcription length is longer than 200kb, plays an important role in many important biological processes in higher organisms. They usually function through mutual regulation with multiple functional genes, and their abnormalities can lead to the formation of many diseases, such as cancer. Among them, the extremely long intergenic noncoding RNA(Very Long Integenic Non-Coding RNAsvlincRNAs1 is a special kind of long chain noncoding RNAs. The present research results have shown that it is involved in the process of early embryonic development and carcinogenesis. But there are still potential functions that have not been confirmed. VlincRNAs provide a new direction for the early stage of cancer development. Given the large number of undiscovered LNC-and vlincRNAs and their role in various cellular physiological activities these transcripts may hold the key to cell development or carcinogenesis. Moreover, more and more studies have shown that lncRNAs play an important role in the action of anticancer drugs. Therefore, these transcription products may be related to the molecular mechanism of many anticancer drugs. In order to understand the function of vlincRNAs, we studied the effect of anticancer drugs on the expression of vlincRNAs. Specifically, we sequenced the RNA of human leukemia cell K562 treated with various anticancer drugs using single molecular sequencing platform, and analyzed the sequencing results to screen vlinc RNAs. This paper focuses on two anticancer drugs-imatinide Gleevec) and smectini. Among them, imatinib is recognized as a good therapeutic and high-volume anticancer drug, and smectini is still in the experimental stage of anticancer drugs. I found that there were significant changes in the expression of some vlincRNAs in K562 cells treated with these two drugs. In addition, I have confirmed that KVUG1KVUG2 and KVUG3 may be involved in the cell proliferation, metabolism and cellular immunity regulated by imatinib.
【学位授予单位】：华侨大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96

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