Key Laboratory of Arrhythmias of The Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Mol Med Rep. 2019 Jan;19(1):638-650. doi: 10.3892/mmr.2018.9695. Epub 2018 Nov 26.
Circular RNAs (circRNAs) are non-coding RNAs forming closed-loop structures, and their aberrant expression may lead to disease. However, the potential network of circRNA‑associated competing endogenous RNA (ceRNA) involved in nonvalvular persistent atrial fibrillation (NPAF) has not been previously reported. In the present study, four left atrial appendages (LAA) of patients with NPAF and four normal LAAs were examined via RNA sequencing, and their potential functions were investigated via bioinformatics analysis. The circRNA‑enriched genes were analyzed using Gene Ontology (GO) categories, while the enrichment of circRNAs was detected via the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A total of 296 significantly dysregulated circRNA transcripts were obtained, with 238 upregulated and 58 downregulated. A number of circRNAs were further confirmed using reverse transcription‑quantitative polymerase chain reaction analysis. Furthermore, the more comprehensive circRNA‑associated ceRNA networks were examined in patients with NPAF. GO categories and KEGG annotation analysis of circRNAs revealed that the circRNA‑associated ceRNA networks were likely to influence AF though alterations in calcium and cardiac muscle contraction. The circRNA‑associated ceRNA networks revealed that dysregulated circRNAs in NPAF may be involved in regulating hsa‑microRNA (miR)‑208b and hsa‑miR‑21. To the best of our knowledge, this study presents the circRNA‑associated ceRNA networks in NPAF for the first time, which may have potential implications for the pathogenesis of AF. This study reveals a potential perspective from which to investigate circRNAs in circRNA‑associated ceRNA networks (hsa_circRNA002085, hsa_circRNA001321) in NPAF, and provides a potential biomarker for AF.
环状 RNA(circRNA)是形成闭环结构的非编码 RNA,其异常表达可能导致疾病。然而,非瓣膜性持续性心房颤动(NPAF)中circRNA 相关竞争性内源 RNA(ceRNA)的潜在网络尚未有报道。在本研究中,通过 RNA 测序检测了 4 例 NPAF 患者和 4 例正常左心耳(LAA)的四个左心耳,并通过生物信息学分析研究了它们的潜在功能。使用基因本体论(GO)类别分析富集的 circRNA 基因,同时通过京都基因与基因组百科全书(KEGG)数据库检测 circRNA 的富集。获得了 296 个显著差异表达的 circRNA 转录本,其中 238 个上调,58 个下调。使用逆转录-定量聚合酶链反应(RT-qPCR)分析进一步证实了一些 circRNA。此外,还在 NPAF 患者中检测了更全面的 circRNA 相关 ceRNA 网络。GO 类别和 KEGG 注释分析 circRNA 表明,circRNA 相关 ceRNA 网络可能通过改变钙和心肌收缩影响 AF。circRNA 相关 ceRNA 网络表明,NPAF 中失调的 circRNA 可能参与调节 hsa-微小 RNA(miR)-208b 和 hsa-miR-21。据我们所知,本研究首次提出了 NPAF 中的 circRNA 相关 ceRNA 网络,这可能对 AF 的发病机制具有潜在意义。本研究揭示了一个潜在的视角,可以从环状 RNA 相关 ceRNA 网络(hsa_circRNA002085、hsa_circRNA001321)研究环状 RNA 在 NPAF 中的作用,并为 AF 提供了一个潜在的生物标志物。