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基于生物信息学分析,长链非编码RNA Snhg1在大鼠肝移植术后急性排斥反应中通过隔离rno-miR-139-5p发挥竞争性内源RNA的重要作用。

LncRNA Snhg1 Plays an Important Role Sequestering rno-miR-139-5p to Function as a ceRNA in Acute Rejection After Rat Liver Transplantation Based on the Bioinformatics Analysis.

作者信息

Wu Wu, Wang Menghao, Li Chunming, Zhu Zhu, Zhang Yang, Wu Di, Ou Zhibing, Liu Zuojin

机构信息

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of Gastrointestinal Surgery, Chengdu Seventh People's Hospital, Chengdu, China.

出版信息

Front Genet. 2022 Jun 2;13:827193. doi: 10.3389/fgene.2022.827193. eCollection 2022.

Abstract

In order to explore the molecular mechanism of acute rejection after liver transplantation (ARLT) in rats, we employed the GSE36798 data set in the Gene Expression Omnibust (GEO) database to construct a related ceRNA network. This dataset contained a total of 16 samples (8 graft samples and 8 plasma samples). Each kind of sample was divided into acute rejection (AR) groups and non-acute rejection (NR) groups, and each group had 4 replicates. First, we performed principal component analysis (PCA) with downloaded data to compare the difference between samples in a macroscopic way. Then, we used the "limma" R package to screen out differentially expressed miRNAs among different groups and used the "pheatmap" R package to perform bidirectional hierarchical clustering analysis for these differentially expressed miRNAs. The miRWalk database and the LncBase V.2 database were applied to predict downstream target genes and upstream-related lncRNAs, respectively. Meanwhile, the String database was used to predict the relationship between target genes, and the aforementioned results were processed for visualization by Cytoscape software. In addition, we exhibited the ultimate ceRNA network, including two lncRNAs, two miRNAs, and 77 mRNAs. Finally, we constructed a rat model of ARLT and applied graft specimens to relevant experimental verification. We found that the lncRNA Snhg1/rno-miR-139-5p axis might be involved in the regulation of ARLT in rats. In short, we demonstrated the differentially expressed miRNA profile, constructed a related ceRNA network, and screened out a possible regulatory axis. In view of the conservation of genes among species, this work was expected to provide a new strategy for the treatment and prevention of ARLT in the clinical setting.

摘要

为了探究大鼠肝移植术后急性排斥反应(ARLT)的分子机制,我们利用基因表达综合数据库(GEO)中的GSE36798数据集构建了一个相关的竞争性内源RNA(ceRNA)网络。该数据集共包含16个样本(8个移植组织样本和8个血浆样本)。每种样本均分为急性排斥反应(AR)组和非急性排斥反应(NR)组,每组有4个重复样本。首先,我们对下载的数据进行主成分分析(PCA),以宏观方式比较样本间的差异。然后,我们使用“limma”R包筛选出不同组间差异表达的微小RNA(miRNA),并使用“pheatmap”R包对这些差异表达的miRNA进行双向层次聚类分析。分别应用miRWalk数据库和LncBase V.2数据库预测下游靶基因和上游相关的长链非编码RNA(lncRNA)。同时,使用String数据库预测靶基因之间的关系,并通过Cytoscape软件对上述结果进行可视化处理。此外,我们展示了最终的ceRNA网络,包括两个lncRNA、两个miRNA和77个信使核糖核酸(mRNA)。最后,我们构建了ARLT大鼠模型,并将移植组织标本应用于相关实验验证。我们发现lncRNA Snhg1/rno-miR-139-5p轴可能参与大鼠ARLT的调控。简而言之,我们展示了差异表达的miRNA谱,构建了相关的ceRNA网络,并筛选出了一条可能的调控轴。鉴于物种间基因的保守性,这项工作有望为临床治疗和预防ARLT提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7da2/9203122/ce9605eaa3e6/fgene-13-827193-g001.jpg

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