整合分析揭示阵发性和持续性心房颤动患者中关键的 mRNA、长非编码 RNA (lncRNA) 和环状 RNA (circRNA)。
Integrative analysis reveals essential mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation patients.
机构信息
Department of Cardiovascular Surgery, the First Affiliated Hospital of Nanjing Medical University; Jiangsu-China.
Department of Cardiothoracic Surgery, Changzhou Wujin People's Hospital; Jiangsu-China.
出版信息
Anatol J Cardiol. 2021 Jun;25(6):414-428. doi: 10.14744/AnatolJCardiol.2020.57295.
OBJECTIVE
This study aimed to investigate the functions of mRNA, long non-coding RNA (lncRNA), and circular RNA (circRNA) in paroxysmal and persistent atrial fibrillation (AF) patients.
METHODS
A total of 9 left atrial appendage (LAA) tissues were collected from patients with AF (ParoAF patients = 3 and PersAF patients = 3) and donors (n=3). Genes and circRNAs were identified by per kilobase per million reads (RPKM) and number of circular reads/number of mapped reads/read length (SRPBM), respectively. Differentially expressed mRNAs (DE mRNAs), lncRNAs (DE lncRNAs), and circRNAs (DE circRNAs) were identified by | log2 (Fold Change) | ≥ 2 and p-value < 0.05. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Protein-protein, mRNA-lncRNA, and circRNA-miRNA interaction networks were constructed. In addition, logistic analysis was conducted among AF and circRNAs.
RESULTS
A total of 285 (116 up-regulated and 169 down-regulated) and 275 (110 up-regulated and 165 down-regulated) DE mRNAs, 575 (276 up-regulated and 299 down-regulated) and 583 (330 up-regulated and 253 down-regulated) DE lncRNAs, and 83 (48 up-regulated and 35 down-regulated) and 99 (58 up-regulated and 41 down-regulated) circRNAs were detected in ParoAF and PersAF, respectively, as compared with control. MAPK signal pathway as well as voltage-dependent, L type, and alpha 1C subunit calcium channel (CACNA1C) might participate in AF occurrence by preventing atrial parasympathetic remodeling. Collagen type I alpha 1 (COL1A1) and COL1A2 mostly participated in the enriched GO and KEGG terms and connected with most of the DE mRNAs. The expression of chr10: 69902697|69948883 was a protective factor against PersAF after adjusting for age (p=0.022, 95% CI: 0.003-0.634).
CONCLUSION
We found that some mRNAs, lncRNAs, circRNAs, and pathways play essential roles in AF pathogenesis and development. Moreover, one protective factor against PersAF was detected.
目的
本研究旨在探讨 mRNA、长链非编码 RNA（lncRNA）和环状 RNA（circRNA）在阵发性和持续性心房颤动（AF）患者中的功能。
方法
共收集 9 例左心耳（LAA）组织标本，分别来自阵发性 AF（ParoAF 患者=3 例，持续 AF 患者=3 例）和供体（n=3）。采用每千碱基每百万读段（RPKM）和环状读段数/映射读段数/读段长度（SRPBM）分别鉴定基因和 circRNA。差异表达的 mRNAs（DE mRNAs）、lncRNAs（DE lncRNAs）和 circRNAs（DE circRNAs）的筛选标准为|log2（Fold Change）|≥2 和 p 值<0.05。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。构建蛋白-蛋白、mRNA-lncRNA 和 circRNA-miRNA 相互作用网络。此外，还进行了 AF 与 circRNAs 之间的逻辑分析。
结果
与对照组相比，ParoAF 和 PersAF 中分别检测到 285 个（116 个上调和 169 个下调）和 275 个（110 个上调和 165 个下调）DE mRNAs、575 个（276 个上调和 299 个下调）和 583 个（330 个上调和 253 个下调）DE lncRNAs、83 个（48 个上调和 35 个下调）和 99 个（58 个上调和 41 个下调）circRNAs。MAPK 信号通路以及电压依赖性、L 型和 alpha 1C 亚基钙通道（CACNA1C）可能通过预防心房副交感神经重塑参与 AF 的发生。I 型胶原 alpha 1（COL1A1）和 COL1A2 主要参与了富集的 GO 和 KEGG 术语，并与大多数 DE mRNAs 相连。在调整年龄后（p=0.022，95%CI：0.003-0.634），chr10:69902697|69948883 的表达是对 PersAF 的保护性因素。
结论
我们发现一些 mRNAs、lncRNAs、circRNAs 和途径在 AF 的发病机制和发展中起着重要作用。此外，还检测到了一个对 PersAF 的保护性因素。
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