关键词: Atrial fibrillation Bioinformatics Epicardial fat Sequencing tRFs & tiRNAs

来  源:   DOI:10.1016/j.heliyon.2024.e30295   PDF(Pubmed)

Abstract:
The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.
摘要:
房颤(AF)的确切过程仍不清楚。有人认为,心外膜脂肪组织(EAT)可能有助于心律失常,并可以释放各种生物活性分子,包括含有tRNA衍生的小RNA(tsRNA)的外泌体。大量研究表明,这些tsRNA可以显著影响关键的细胞功能。然而,目前没有研究调查来自EAT和AF的tsRNA之间的关系。为了探讨EAT与AF相关的tsRNAs的调控机制,我们对6例房颤患者和6例窦性心律对照组的EAT样本进行了RNA测序分析.我们的分析揭示了在AF中146个tsRNA的上调和126个tsRNA的下调。此外,我们随机选择4种tsRNA(tRF-SeC-TCA-001,tiRNA-Gly-CCC-003,tRF-Gly-GCC-002和tRF-Tyr-GTA-007)进行定量逆转录-聚合酶链反应验证.在此之后,生物信息学分析显示,这些tsRNA的靶基因显著参与了细胞粘附和质膜粘附分子介导的各种细胞过程的调节。此外,基于KEGG分析,研究表明,这些靶基因中的大多数可能通过糖胺聚糖生物合成等过程参与AF的发病,AMP激活的蛋白激酶活性,和胰岛素信号通路。我们的结果阐明了从AF患者获得的EAT样本中tsRNA表达谱的变化,他们预测了潜在的靶基因以及EAT中tsRNA和mRNA之间的相互作用,这些相互作用可能有助于AF的发病机理。
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