| 王芬芬,郭丽,彭成明,李军,温志立.基于转录组测序技术揭示克罗恩病中相关的可变剪接事件[J].井冈山大学自然版,2023,44(6):53-60 |
| 基于转录组测序技术揭示克罗恩病中相关的可变剪接事件 |
| TRANSCRIPTOME ANALYSIS OF ALTERNATIVE SPLICING EVENTS IN CROHN’S DISEASE |
| 投稿时间：2023-09-16 修订日期：2023-10-28 |
| DOI：10.3969/j.issn.1674-8085.2023.06.007 |
| 中文关键词: 转录组分析 克罗恩病 可变剪接 RNA结合蛋白 |
| 英文关键词: transcriptome analysis Crohn's disease alternative splicing RNA-binding proteins |
| 基金项目:国家自然科学基金面上项目(82070594);江西省自然科学基金青年项目(20224BAB216020) |
| 作者 | 单位 | | 王芬芬 | 南昌大学第二附属医院, 江西, 南昌 330006 | | 郭丽 | 南昌大学第二附属医院, 江西, 南昌 330006 | | 彭成明 | 南昌大学第二附属医院, 江西, 南昌 330006 | | 李军 | 南昌大学第二附属医院, 江西, 南昌 330006 | | 温志立 | 南昌大学第二附属医院, 江西, 南昌 330006 |
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| 中文摘要: |
| 通过利用转录组测序分析了解克罗恩病(Crohn’s disease,CD)相关的可变剪接事件,鉴定高度关联的RNA结合蛋白及潜在的调控靶基因,以揭示CD形成过程中相关遗传调控机制。通过下载33个GSE66207RNA-seq数据并进行预处理,其中包括6个非狭窄非穿透型(B1型)样品、6个狭窄型(B2型)样品、8个穿透/瘘管型(B3型)样品和13个正常结肠样品;对四组样品进行差异表达基因和可变剪接事件转录组分析、进行差异表达RNA结合蛋白与差异可变剪接基因之间的相关性分析。结果显示:(1)通过差异表达基因的转录组分析发现,以正常组为参考,B1型更多基因表现为下调,B2型和B3型更多基因表现为上调。B3型的差异表达基因数量比B2型多,暗示着CD病情进展为穿透后,更多基因会出现差异表达;(2)差异可变剪接转录组分析发现,CD中存在大量剪接异常,并发生在DNA复制和细胞周期进展中。GO功能注释和富集分析显示,在B1型、B2型和B3型中,参与细胞生长的基因都发生剪接异常,在B2型和B3型中发现明显的凋亡相关通路。(3)鉴定出14个调控差异可变剪接基因的RNA结合蛋白,包括:DAZL、DDX3Y、RPS4Y1、EIF1AY、TDRD1、RBM24、RNASE2、APOBEC1、NXF3、EEF1A2、RBFOX3、PALYL、RNF17和OASL。本研究对3种表型CD进行可变剪接分析发现:在CD疾病进展中,一些参与细胞增殖、凋亡和关键信号通路的基因发生了差异可变剪接,而实验研究鉴定出的RNA结合蛋白参与了这些可变剪接基因的调控。 |
| 英文摘要: |
| Transcriptome sequencing analysis was used to understand the alternative splicing events of Crohn's disease(CD), and to identify highly associated RNA binding proteins and potential regulatory genes, so as to reveal the genetic regulatory mechanisms during CD formation. We downloaded and preprocessed 33 published transcriptome sequencing data(GSE66207 RNA-seq)of colon tissues from CD patients with three different disease behaviors, including 6 nonstricturing and nonpe-netrating(B1), 6 stricturing(B2), and 8 penetrating/fistulizing(B3), and that of 13 non-IBD controls(Nor).We performed transcriptome analysis of differentially expressed genes and alternative splicing events, and correlation analysis between the differentially expressed RBP and differential alternative splicing genes associated with CD.Resultsshow:(1) Analysis of the number of differentially expressed genes found that more B1 genes were down-regulated, and more B2 and B3 genes were up-regulated. The number of differentially expressed genes in B3 is larger than that of B2, suggesting that more genes are differentially expressed after the disease progressing into penetration.(2) A large number of abnormal alternative splicing occur in DNA replication and cell cycle progression in CD. GO analysis showed that the abnormal alternative splicing genes involved in cell growth in B1, B2 and B3, and obvious apoptosis-related pathways were found in B2 and B3.(3) Fourteen RNA-binging proteins(DAZL, DDX3Y, RPS4Y1, EIF1AY,TDRD1, RBM24, RNASE2, APOBEC1, NXF3, EEF1A2, RBFOX3, PALYL, RNF17, and OASL) were identified as involved in the regulation of alternative splicing of related genes in CD. In this study, we performed gene alternative splicing analysis of three phenotype CD, and found that a number of genes involved in cell proliferation, apoptosis and key signaling pathways undergo abnormal splicing regulated by 14 RNA binding proteins in CD progression. |
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