Identification of atrial fibrillation-associated lncRNAs and exploration of their functions based on WGCNA and ceRNA network analyses
Identification of atrial fibrillation-associated lncRNAs and exploration of their functions based on WGCNA and ceRNA network analyses
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基于WGCNA和ceRNA网络分析识别房颤相关lncRNA并探索其功能
DOI：
10.4149/gpb_2021015
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发表时间：
2021-01-01
影响因子：
1.5
通讯作者：
Jiao, Zhanquan
中科院分区：
文献类型：
--
作者：
Liu, Yanhong;Liang, Xue;Jiao, Zhanquan
房颤(房颤)是一种常见的心律失常，可导致严重的并发症。然而，房颤的药物治疗仍然具有挑战性。本研究旨在利用基因表达数据库中收集的基因芯片数据集(LncRNAs和mRNAs：GSE79768，GSE115574；miRNAs：GSE68475)筛选与房颤相关的关键的长非编码RNAs(LncRNAs)、微RNAs(MiRNAs)和信使RNA(MRNAs)。对GSE79768和GSE115574数据集进行加权相关网络分析，发现5个模块与房颤状态高度相关。在118个与模块相关的差异表达基因中，根据蛋白质相互作用网络中节点的基因重要性、模块成员关系和拓扑特征，认为FBXW7、EGFR、CXCR2、ROCK1和UBE2D1是中枢基因。LncRNA MIR100HG和LINC01105可能通过与(MIR100HG-ROCK1/FBXW7/UBE2D1，LINC01105-EGFR)mRNAs共表达或海绵miRNAs调节mRNAs(LINC01105-miR-125a-3p-EGFR，MIR100HG-miR-200b-3pFBXW7，MIR100HG-miR-561-3p-CXCR2，MIR100HG-miR-548z-UBE2D1)发挥作用。连接图谱和比较毒理基因组学数据库搜索预测地塞米松可能通过逆转MIR100HG的表达来治疗房颤；青蒿素可能逆转HUB DGs的表达。综上所述，我们的研究结果可能为房颤的治疗提供新的分子机制和潜在的治疗靶点和药物。
Atrial fibrillation (AF) is a common cardiac arrhythmia that induces serious complications. However, pharmacological treatments of AF remain challenging. This study aimed to screen crucial long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) for AF using the microarray datasets (lncRNAs and mRNAs: GSE79768, GSE115574; miRNAs: GSE68475) collected from the Gene Expression Omnibus database. Weighted correlation network analysis of GSE79768 and GSE115574 datasets identified five modules were highly related to AF status. Among 118 module-related differentially expressed mRNAs, FBXW7, EGFR, CXCR2, ROCK1 and UBE2D1 were considered as hub genes according to the gene significance, module membership and the topological characteristics for the nodes in the protein-protein interaction network. lncRNA MIR100HG and LINC01105 may function by co-expressing with (MIR100HG-ROCK1/FBXW7/UBE2D1, LINC01105-EGFR) mRNAs or sponging miRNAs to regulate mRNAs (LINC01105-miR-125a-3p-EGFR, MIR100HG-miR-200b-3pFBXW7, MIR100HG-miR-561-3p-CXCR2, MIR100HG-miR-548z-UBE2D1). Connectivity Map and Comparative Toxicogenomics Database searches predicted dexamethasone may treat AF by reversing the expression of MIR100HG; artemisinin may reverse the expression of hub DEGs. In conclusion, our results may provide novel molecular mechanisms and potential therapeutic targets and drugs for AF.