Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves’ disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves’ disease.

中文翻译：

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格雷夫斯病中差异表达的血浆外泌体环状RNA的微阵列分析和功能分析。

循环RNA（circRNA）调节细胞中的各种生物活性。对外泌体circRNA的更好理解可以为Graves病（GD）的发病机理和治疗提供新的见解。我们旨在分析GD患者血浆外泌体中差异表达的circRNA（DEcRs），并通过全面的生物信息学分析推测和探查DEcR的功能。通过超速离心从5名原发性GD患者和5名健康对照中分离出血清外泌体。用透射电子显微镜验证后，使用人circRNA微阵列对外泌体样品进行微阵列分析。使用逆转录酶定量聚合酶链反应（RT-qPCR），选择了两个上调的DEcRs和两个下调的DEcRs在来自20 GD和20名健康对照参与者的血浆外泌体中进行验证。然后组装circRNA / microRNA / mRNA相互作用网络，并利用基因本体论和KEGG（基因和基因组京都百科全书）途径的分析来预测DEcR相关基因的潜在功能。在原发性GD病例中发现了15个DEcR。内含子circRNA hsa_circRNA_000102被确认为GD患者血浆外泌体中的上调成分。circRNA / microRNA / mRNA相互作用网络揭示了hsa_circRNA_000102及其相关基因最有潜力的靶向microRNA。功能分析预测hsa_circRNA_000102相关基因参与免疫系统激活的途径，例如病毒感染和β-干扰素信号传导。hsa_circRNA_000102是GD患者血浆外体circRNA的差异上调。我们的研究突出了介导Graves病免疫激活的多种途径，尤其是病毒感染和β干扰素信号传导。