Department of Cardiology, Qingdao Municipal Hospital, Qingdao University, No. 5, Donghai Middle Road, Qingdao, 266071, Shandong, China.
Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, No. 5, Donghai Middle Road, Qingdao, 266071, Shandong, China.
Eur J Med Res. 2024 Apr 20;29(1):244. doi: 10.1186/s40001-024-01799-3.
Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation.
We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments.
A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of "regulation of immune response" and "regulation of immune system process", the cellular components (CCs) of "extracellular matrix" and "cell‒cell junction", and the molecular functions (MFs) of "signaling adaptor activity" and "protein-macromolecule adaptor activity". According to the KEGG analysis, the DEGs were associated with the "PI3K-Akt signaling pathway" and "MAPK signaling pathway." Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2.
The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.
心房颤动（AF）是全球最常见的心律失常。导管消融已成为 AF 的重要治疗方法。然而，导管消融后仍有可能出现 AF 复发。我们的研究旨在阐明长链非编码 RNA-mRNA 调控网络在导管消融后晚期 AF 复发中的作用。
我们对 5 例 AF 消融后有复发（P-RAF）和 5 例 AF 消融后无复发（A-RAF）的样本进行了 RNA 测序，以分析转录组。使用 DESeq2 R 包分析差异表达基因（DEGs）和长链非编码 RNA（DE-lncRNAs）。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析评估 DEGs 的功能相关性。使用 STRING 和 Cytoscape 构建蛋白质-蛋白质相互作用（PPI）网络。我们还使用 BEDTools v2.1.2 软件和 Pearson 相关系数方法建立了 DE-lncRNAs 和 DEGs 之间的 lncRNA-mRNA 调控网络。为了验证枢纽基因的高通量测序结果，我们进行了定量实时聚合酶链反应（qRT-PCR）实验。
共检测到 28528 个 mRNAs 和 42333 个 lncRNAs。两组间共鉴定出 96 个 DEGs 和 203 个 DE-lncRNAs。GO 分析显示，DEGs 在“免疫反应的调节”和“免疫系统过程的调节”的生物学过程（BP）、“细胞外基质”和“细胞-细胞连接”的细胞成分（CC）以及“信号适配器活性”和“蛋白质-大分子适配器活性”的分子功能（MF）中富集。根据 KEGG 分析，DEGs 与“PI3K-Akt 信号通路”和“MAPK 信号通路”有关。通过 PPI 网络鉴定出 9 个枢纽基因（MMP9、IGF2、FGFR1、HSPG2、GZMB、PEG10、GNLY、COL6A1 和 KCNE3）。lncRNA-TMEM51-AS1-201 被确定为 lncRNA-mRNA 调控网络中的核心调节剂，表明其通过调节 COL6A1、FGFR1、HSPG2 和 IGF2 对导管消融后 AF 的复发可能具有潜在影响。
导管消融后心房颤动的复发可能与免疫反应和纤维化有关，细胞外基质起着关键作用。TMEM51-AS1-201 已被确定为导管消融后 AF 复发的潜在关键靶点。
