基于竞争性内源性RNA的心房颤动lncRNA-miRNA-mRNA网络综合分析
Integrated analysis of the lncRNA-miRNA-mRNA network based on competing endogenous RNA in atrial fibrillation.
作者信息
Wang Manman, An Guoying, Wang Benxuan, Chen Yuanyuan, Liu Genli, Wang Xin, Liu Shuai, Zhang Daozou, Sun Dandan, Zhang Yanyan, Shen Tong, Li Xiangting
机构信息
Jining Key Laboratory for Diagnosis and Treatment of Cardiovascular Diseases, Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining, China.
Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Department of Cardiac Surgery, Affiliated Hospital of Jining Medical University, Jining, China.
出版信息
Front Cardiovasc Med. 2023 Apr 27;10:1099124. doi: 10.3389/fcvm.2023.1099124. eCollection 2023.
OBJECTIVE
Long non-coding RNAs (lncRNAs) play pivotal roles in the transcriptional regulation of atrial fibrillation (AF) by acting as competing endogenous RNAs (ceRNAs). In the present study, the expression levels of lncRNAs of sinus rhythm (SR) patients and AF patients were investigated with transcriptomics technology, and the lncRNA-miRNA-mRNA network based on the ceRNA theory in AF was elaborated.
METHODS
Left atrial appendage (LAA) tissues were obtained from patients with valvular heart disease during cardiac surgery, and they were divided into SR and AF groups. The expression characterizations of differentially expressed (DE) lncRNAs in the two groups were revealed by high-throughput sequencing methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the lncRNA-miRNA-mRNA-mediated ceRNA network was constructed.
RESULTS
A total of differentially expressed 82 lncRNAs, 18 miRNAs, and 495 mRNAs in human atrial appendage tissues were targeted. Compared to SR patients, the following changes were found in AF patients: 32 upregulated and 50 downregulated lncRNAs; 7 upregulated and 11 downregulated miRNAs; and 408 upregulated and 87 downregulated mRNAs. A lncRNA-miRNA-mRNA network was constructed, which included 44 lncRNAs, 18 miRNAs, and 347 mRNAs. qRT-PCR was performed to verify these findings. GO and KEGG analyses suggested that inflammatory response, chemokine signaling pathway, and other biological processes play important roles in the pathogenesis of AF. Network analysis based on the ceRNA theory identified that lncRNA XR_001750763.2 and Toll-like receptor 2 (TLR2) compete for binding to miR-302b-3p. In AF patients, lncRNA XR_001750763.2 and TLR2 were upregulated, and miR-302b-3p was downregulated.
CONCLUSION
We identified a lncRNA XR_001750763.2/miR-302b-3p/TLR2 network based on the ceRNA theory in AF. The present study shed light on the physiological functions of lncRNAs and provided information for exploring potential treatments for AF.
目的
长链非编码RNA（lncRNAs）作为竞争性内源RNA（ceRNAs），在心房颤动（AF）的转录调控中起关键作用。在本研究中，运用转录组学技术研究窦性心律（SR）患者和AF患者lncRNAs的表达水平，并构建基于ceRNA理论的AF中的lncRNA- miRNA- mRNA网络。
方法
在心脏手术期间从心脏瓣膜病患者获取左心耳（LAA）组织，并将其分为SR组和AF组。通过高通量测序方法揭示两组中差异表达（DE）lncRNAs的表达特征。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，并构建lncRNA- miRNA- mRNA介导的ceRNA网络。
结果
共靶向人左心耳组织中差异表达的82个lncRNAs、18个miRNAs和495个mRNAs。与SR患者相比，AF患者出现以下变化：32个lncRNAs上调，50个lncRNAs下调；7个miRNAs上调，11个miRNAs下调；408个mRNAs上调，87个mRNAs下调。构建了一个lncRNA- miRNA- mRNA网络，其中包括44个lncRNAs、18个miRNAs和347个mRNAs。进行qRT-PCR以验证这些结果。GO和KEGG分析表明，炎症反应、趋化因子信号通路和其他生物学过程在AF的发病机制中起重要作用。基于ceRNA理论的网络分析确定lncRNA XR_001750763.2和Toll样受体2（TLR2）竞争与miR-302b-3p结合。在AF患者中，lncRNA XR_001750763.2和TLR2上调，而miR-302b-3p下调。
结论
我们基于ceRNA理论在AF中鉴定出一个lncRNA XR_001750763.2/miR-302b-3p/TLR2网络。本研究揭示了lncRNAs的生理功能，并为探索AF的潜在治疗方法提供了信息。
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