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利用纳米递送技术鉴定心房颤动中的竞争性内源RNA调控网络

Identification of CeRNA Regulatory Networks in Atrial Fibrillation Using Nanodelivery.

作者信息

Lin Ping, Meng Lingqiang, Lyu Lei

机构信息

Department of Cardiology, Dongying Traditional Chinese Medicine Hospital, Dongying 257055, Shandong, China.

Department of Laboratory, Dongying Traditional Chinese Medicine Hospital, Dongying 257055, Shandong, China.

出版信息

Evid Based Complement Alternat Med. 2022 Sep 29;2022:1046905. doi: 10.1155/2022/1046905. eCollection 2022.

Abstract

The initiation and maintenance of AF is a complex biological process that is the ultimate manifestation of many cardiovascular diseases. And the pathogenesis of atrial fibrillation (AF) is unclear. Therefore, this study aimed to find the potential competing endogenous RNAs (ceRNAs) network and molecular dysregulation mechanism associated with AF. GSE135445, GSE2240, and GSE68475 were obtained from the Gene Expression Omnibus (GEO). Differential analysis was utilized to identify the differentially expressed mRNAs, miRNAs, and lncRNAs between AF and sinus rhythms (SR). AF-associated mRNAs and nanomaterials were screened and their biological functions and KEGG signaling pathways were identified. Nanomaterials for targeted delivery are uniquely capable of localizing the delivery of therapeutics and diagnostics to diseased tissues. The target mRNAs and target lncRNAs of differentially expressed miRNAs were identified using TargetScan and LncBase databases. Finally, we constructed the ceRNAs network and its potential molecular regulatory mechanism. We obtained 643 AF-associated mRNAs. They were significantly involved in focal adhesion and the PI3K-Akt signaling pathway. Among the 16 differentially expressed miRNAs identified, 31 differentially expressed target mRNAs, as well as 5 differentially expressed target lncRNAs were identified. Among them, we obtained 2 ceRNAs networks (hsa-miR-125a-5p and hsa-let-7a-3p). The aberrant expression of network target genes in AF mainly activated the HIF-1 signaling pathway. We speculated that the interaction pairs of miR-125a-5p and let-7a-3p with target mRNAs and target lncRNAs may be involved in AF. Our findings have a positive influence on investigating the pathogenesis of AF and identifying potential therapeutic targets.

摘要

房颤的起始与维持是一个复杂的生物学过程,是多种心血管疾病的最终表现形式。而且房颤的发病机制尚不清楚。因此,本研究旨在寻找与房颤相关的潜在竞争性内源RNA(ceRNA)网络及分子失调机制。从基因表达综合数据库(GEO)获取了GSE135445、GSE2240和GSE68475。利用差异分析来鉴定房颤与窦性心律(SR)之间差异表达的mRNA、miRNA和lncRNA。筛选出与房颤相关的mRNA和纳米材料,并确定其生物学功能和KEGG信号通路。用于靶向递送的纳米材料具有独特的能力,能够将治疗药物和诊断试剂递送至病变组织。使用TargetScan和LncBase数据库鉴定差异表达miRNA的靶mRNA和靶lncRNA。最后,我们构建了ceRNA网络及其潜在的分子调控机制。我们获得了643个与房颤相关的mRNA。它们显著参与粘着斑和PI3K-Akt信号通路。在鉴定出的16个差异表达miRNA中,确定了31个差异表达的靶mRNA以及5个差异表达的靶lncRNA。其中,我们获得了2个ceRNA网络(hsa-miR-125a-5p和hsa-let-7a-3p)。房颤中网络靶基因的异常表达主要激活了HIF-1信号通路。我们推测miR-125a-5p和let-7a-3p与靶mRNA和靶lncRNA的相互作用对可能参与了房颤。我们的研究结果对研究房颤的发病机制和确定潜在治疗靶点具有积极影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d79/9536897/4abf1f373ec7/ECAM2022-1046905.001.jpg

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