Fan Yuexin, Zheng Yang, Wang Jiahui, Zhao Tiejian, Liang Tianjian
School of Mathematical Sciences, Dalian University of Technology Dalian 116024, Liaoning, China.
Department of Medicine, Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine Nanning 530222, Guangxi, China.
Int J Clin Exp Pathol. 2020 Nov 1;13(11):2820-2830. eCollection 2020.
This study investigates the expression profile of circRNA in nonalcoholic steatohepatitis (NASH) cirrhosis and identifies the underlying pathogenesis of core genes of NASH cirrhosis.
The GEO 134146 dataset was obtained from GEO database. EdgeR software was used to analyze the differential expression of circRNA between NASH cirrhosis samples and normal samples, and Starbase and miRWalk databases were used to predict the targeted miRNA and mRNA. The protein-protein interaction network of these target genes was established by searching the string database of interacting genes, Cytoscape and Mcode analysis. In addition, David and Omicshare were used to analyze the functional enrichment and pathway enrichment of target genes.
We evaluated 99 differentially expressed circRNAs, 27 of which were up-regulated, and 72 were down-regulated. A regulatory network consisting of 10 circRNAs, 30 miRNAs, and 1217 mRNAs was further constructed. The differential expression of circRNA is closely related to the functions of "target gene transcriptional regulation", "protein binding", "serine/threonine kinase", etc. The difference in circRNA is mainly related to the "MAPK" signaling pathway and the "FoxO" signaling pathway.
This study confirmed the abnormal regulation of circRNA in NASH cirrhosis. Bioinformatic analysis showed that abnormal expression of circRNA might be related to the occurrence and development of NASH cirrhosis.
本研究调查非酒精性脂肪性肝炎(NASH)肝硬化中环状RNA(circRNA)的表达谱,并确定NASH肝硬化核心基因的潜在发病机制。
从基因表达综合数据库(GEO)获取GEO 134146数据集。使用EdgeR软件分析NASH肝硬化样本与正常样本之间circRNA的差异表达,并使用Starbase和miRWalk数据库预测靶向的微小RNA(miRNA)和信使核糖核酸(mRNA)。通过搜索相互作用基因的STRING数据库、Cytoscape和Mcode分析建立这些靶基因的蛋白质-蛋白质相互作用网络。此外,使用David和Omicshare分析靶基因的功能富集和通路富集。
我们评估了99个差异表达的circRNA,其中27个上调,72个下调。进一步构建了由10个circRNA、30个miRNA和1217个mRNA组成的调控网络。circRNA的差异表达与“靶基因转录调控”、“蛋白质结合”、“丝氨酸/苏氨酸激酶”等功能密切相关。circRNA的差异主要与“丝裂原活化蛋白激酶(MAPK)”信号通路和“叉头框蛋白O(FoxO)”信号通路有关。
本研究证实了NASH肝硬化中circRNA的异常调控。生物信息学分析表明,circRNA的异常表达可能与NASH肝硬化的发生发展有关。