exoRBase数据库外泌体基因在冠心病中的差异表达及意义
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(北京中医药大学东直门医院,北京市 100700)

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张楠楠,硕士研究生,研究方向为中西医结合临床心血管内科,E-mail为997110541@qq.com。通信作者常佩芬,博士,主任医师,教授,博士研究生导师,研究方向为中西医结合临床心血管内科,E-mail为13661022016@163.com。

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国家自然科学基金面上项目(81973787)


Expression and significance of exosomal genes in coronary heart disease:an analysis based on exoRBase database
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Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China)

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    摘要:

    目的 通过对exoRBase外泌体数据库中筛选出的冠心病(CHD)患者外周血外泌体差异表达基因的分析和CeRNA网络的构建,挖掘导致冠心病发病和疾病进展中的关键基因和调控机制,通过对差异表达mRNA关键基因的GO和KEGG富集分析,研究冠心病差异表达mRNA参与的分子功能和生物学过程。方法 应用R语言筛选出在exoRBase外泌体数据库冠心病患者外周血中差异表达的外泌体基因,通过在线数据库和Cytoscape软件构建CeRNA网络,对关键基因进行可视化分析,并对差异表达的mRNA关键基因进行GO和KEGG富集分析。结果筛选出冠心病患者外周血中差异表达的外泌体mRNA 312个,lncRNA 43个,circRNA 85个;通过构建CeRNA网络,发现mRNA、lncRNA和circRNA竞争性地结合miRNA,且与miRNA相结合的lncRNA表达均显著上调,而mRNA和circRNA的表达则大多数呈现显著下调的趋势;差异表达mRNA关键基因的GO和KEGG富集分析结果显示,这些关键基因主要与“磷酸酶激活活动”和“磷酸酶调节活动”功能相关。结论 由exoRBase数据库筛选出的冠心病患者外周血外泌体与健康人群具有显著差异性,且mRNA、lncRNA和circRNA可以竞争性地和与冠心病显著相关的miRNA相结合,并以之实现相互调控作用。这些基因可能参与了冠心病的发生和发展,可以作为其调控点和治疗药物靶点。

    Abstract:

    Aim Through the exoRBase database to screen the differentially expressed exosomal genes and build the CeRNA network in the peripheral blood of coronary heart disease (CHD), and then explore the key genes and regulatory mechanisms leading to the onset and progression of CHD. Through the key genes of differentially expressed mRNA who were enriched by GO and KEGG analysis, to study the molecular function and biological processes of the differentially expressed mRNA in CHD. Methods The R language was used to screen the differentially expressed exosomal genes in the peripheral blood of CHD, and the online databases and Cytoscape software was used to construct the CeRNA networks.And then visualized and analyzed the key genes. In the end, the GO and KEGG enrichment analysis was performed for the differentially expressed mRNA key genes. Results A total of 312 exosomal mRNA, 43 exosomal lncRNA and 85 exosomal circRNA with differential expressed were screened out from the peripheral blood of CHD patients. Through the construction of the CeRNA network, it was found that mRNA, lncRNA and circRNA competitively bound to miRNA, and the expressions of lncRNA combined with miRNA were significantly up-regulated, while the expressions of mRNA and circRNA were mostly significantly down-regulated. The GO and KEGG enrichment analysis of key genes of differentially expressed mRNA showed that these key genes were mainly related to “phosphatase activator activity” and “phosphatase regulatory activity” functions. Conclusions The peripheral blood exosomes screened by exoRBase database in patients with CHD are significantly different from those in healthy people, and mRNA, lncRNA and circRNA can competitively combine with miRNA significantly related to CHD and achieve mutual regulation. These genes may be involved in the occurrence and development of CHD and can be used as its regulatory points and therapeutic drug targets.

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张楠楠,赵明镜,孔令旗,张艺璇,王尔玉,修晟尧,李天力,刘小芸,贺小芳,常佩芬. exoRBase数据库外泌体基因在冠心病中的差异表达及意义[J].中国动脉硬化杂志,2022,30(1):36~42.

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  • 收稿日期:2021-03-12
  • 最后修改日期:2021-09-26
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  • 在线发布日期: 2022-01-07