Department of Cardiovascular Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China.
Department of Cardiovascular Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust.
Int Heart J. 2021;62(1):153-161. doi: 10.1536/ihj.20-238.
The aim of this study was to explore the pivotal genes or lncRNAs involved in the progression of atrial fibrillation (AF) -valvular heart disease (VHD). The mRNA profiling GSE113013 was obtained from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out for DEGs. Then, the construction of the protein-protein interaction (PPI) network was conducted. An lncRNA-miRNA-target ceRNA network was constructed after obtaining microRNAs (miRNA) related to DElncRNAs. Ultimately, key disease-related genes were screened. A total of 399 DEGs and 145 DElncRNAs were obtained. There were 283 nodes and 588 interaction pairs in the PPI network, and synaptosome-associated protein 25 (SNAP25) had higher degrees (degree = 22) in the PPI network. There were 65 interaction pairs in the ceRNA network. Here, Baculoviral IAP Repeat Containing 5 (BIRC5) was regulated by hsa-miR-1285-3p, which was regulated by lncRNA NPHP3-AS1. Gap Junction Protein Alpha 5 (GAJ5) was regulated by hsa-miR-4505, hsa-miR-1972, and hsa-miR-1199-5p. In particular, GAJ5 was enriched in the function of ion transmembrane transport regulation, whereas BIRC5 was enriched in the function of apoptosis-multiple species pathway. Similarly, Potassium Inwardly Rectifying Channel Subfamily J Member 6 (KCNJ6) was enriched in the function of an ion channel complex. VENN analysis identified BIRC5 and GJA5 as key AF-related genes. KCNJ6, SNAP25, GJA5, BIRC5, hsa-miR-1285-3p, and lncRNA NPHP3-AS1 were likely to be associated with AF-VHD development.
本研究旨在探讨与心房颤动（AF）-瓣膜性心脏病（VHD）进展相关的关键基因或长链非编码 RNA（lncRNA）。从基因表达综合数据库中获取 mRNA 图谱 GSE113013。进行差异表达基因（DEGs）和差异表达长链非编码 RNA（DElncRNA）的鉴定。对 DEGs 进行基因本体论和京都基因与基因组百科全书通路富集分析。然后，构建蛋白质-蛋白质相互作用（PPI）网络。获得与 DElncRNA 相关的 microRNA（miRNA）后，构建 lncRNA-miRNA-靶 ceRNA 网络。最终筛选出关键疾病相关基因。共获得 399 个 DEG 和 145 个 DElncRNA。PPI 网络中有 283 个节点和 588 个相互作用对，PPI 网络中 SNAP25 的度（度=22）较高。ceRNA 网络中有 65 个相互作用对。在这里，Baculoviral IAP Repeat Containing 5（BIRC5）受 hsa-miR-1285-3p 的调控，而 hsa-miR-1285-3p 受 lncRNA NPHP3-AS1 的调控。间隙连接蛋白α 5（GAJ5）受 hsa-miR-4505、hsa-miR-1972 和 hsa-miR-1199-5p 的调控。特别是，GAJ5 富集在离子跨膜运输调节功能中，而 BIRC5 富集在凋亡-多种物种途径的功能中。同样，Potassium Inwardly Rectifying Channel Subfamily J Member 6（KCNJ6）在离子通道复合物的功能中被富集。VENN 分析确定 BIRC5 和 GJA5 为关键的 AF 相关基因。KCNJ6、SNAP25、GJA5、BIRC5、hsa-miR-1285-3p 和 lncRNA NPHP3-AS1 可能与 AF-VHD 的发生发展有关。
