Integrative Analysis Reveals Key Circular RNA in Atrial Fibrillation
Integrative Analysis Reveals Key Circular RNA in Atrial Fibrillation
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综合分析揭示心房颤动中关键的环状RNA
DOI：
10.3389/fgene.2019.00108
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发表时间：
2019-02-19
影响因子：
3.7
通讯作者：
Liu, Xu
中科院分区：
文献类型：
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作者：
Hu, Xiaofeng;Chen, Linhui;Liu, Xu
环状RNA （circRNAs）是一类新兴的RNA物种，可能在基因表达控制中发挥关键的调节作用，由于其丰富、稳定和细胞或组织特异性的表达，可以作为许多疾病的诊断生物标志物。然而，环状rna与心房颤动（AF）之间的关系尚不清楚。在这项研究中，我们使用RNA测序数据来鉴定和量化circrna。circrna的差异表达分析发现，与健康供者相比，AF受试者中分别有250个上调和126个下调的circrna。基因本体（Gene Ontology， GO）和京都基因基因组百科全书（Kyoto Encyclopedia of Genes and Genomes， KEGG）对失调环状rna的亲本基因分析表明，上调的亲本基因可能参与了氧化应激下DNA损伤的过程。此外，为了注释失调的环状RNA，我们分别构建并合并了竞争性内源RNA （ceRNA）网络和蛋白质-蛋白质相互作用（PPI）网络。在合并的网络中，246个失调的环状rna中有130个通过不止一种途径被成功表征。值得注意的是，通过富集分析，chr9:15474007-15490122、chr16:75445723-75448593、hsa_circ_0007256、chr12:56563313-56563992和hsa_circ_0003533这5个circrna表现出最高的显著性，其中4个在细胞因子-细胞因子受体相互作用中富集。这些失调的环状rna可能主要参与炎症反应的生物学过程。总之，本研究确定了一组失调的环状rna，并描述了它们的潜在功能，这可能与AF的炎症反应有关。据我们所知，这是第一个揭示环状rna与AF之间关联的研究，这不仅提高了我们对环状rna在AF中的作用的理解，而且为AF研究人员提供了潜在功能环状rna的候选物。
Circular RNAs (circRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression control, which can serve as diagnostic biomarkers for many diseases due to their abundant, stable, and cell- or tissue-specific expression. However, the association between circRNAs and atrial fibrillation (AF) is still not clear. In this study, we used RNA sequencing data to identify and quantify the circRNAs. Differential expression analysis of the circRNAs identified 250 up- and 126 down-regulated circRNAs in AF subjects compared with healthy donors, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the parental genes of the dysregulated circRNAs indicated that the up-regulated parental genes may participate in the process of DNA damage under oxidative stress. Furthermore, to annotate the dysregulated circRNAs, we constructed and merged the competing endogenous RNA (ceRNA) network and protein-protein interaction (PPI) network, respectively. In the merged network, 130 of 246 dysregulated circRNAs were successfully characterized by more than one pathway. Notably, the five circRNAs, including chr9:15474007-15490122, chr16:75445723-75448593, hsa_circ_0007256, chr12:56563313-56563992, and hsa_circ_0003533, showed the highest significance by the enrichment analysis, and four of them were enriched in cytokine-cytokine receptor interaction. These dysregulated circRNAs may mainly participate in biological processes of inflammatory response. In conclusion, the present study identified a set of dysregulated circRNAs, and characterized their potential functions, which may be associated with inflammatory responses in AF. To our knowledge, this is the first study to uncover the association between circRNAs and AF, which not only improves our understanding of the roles of circRNAs in AF, but also provides candidates of potentially functional circRNAs for AF researchers.