Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves' disease
Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves' disease
复制标题
格雷夫斯病血浆外泌体环状 RNA 差异表达的微阵列分析和功能分析
DOI：
10.1186/s40659-020-00299-y
复制
发表时间：
2020-01-01
影响因子：
6.7
通讯作者：
Zhou, Jin
中科院分区：
文献类型：
--
作者：
Sun, Ying;Wang, Wei;Zhou, Jin
背景循环RNA (circRNA) 调节细胞中的各种生物活性。更好地了解外泌体 circRNA 可以为格雷夫斯病 (GD) 的发病机制和治疗提供新的见解。我们的目的是分析 GD 患者血浆外泌体中差异表达的 circRNA（DEcR），并通过综合生物信息学分析推测和探讨 DEcR 的功能。方法通过超速离心从 5 名原发性 GD 患者和 5 名健康对照中分离血清外泌体。经过透射电子显微镜验证后，外泌体样品使用人类 circRNA 微阵列进行微阵列分析。使用逆转录酶定量聚合酶链式反应 (RT-qPCR)，选择 20 名 GD 和 20 名健康对照参与者的血浆外泌体中的两个上调和两个下调的 DEcR 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（京都基因和基因组百科全书）途径的分析来预测DEcR相关基因的潜在功能。结果 原发性 GD 病例中发现 15 个 DEcR。内含子 circRNA hsa_circRNA_000102 被证实是 GD 患者血浆外泌体中上调的成分。 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途径，例如病毒感染和干扰素-β 信号传导。结论 hsa_circRNA_000102 是 GD 患者血浆外泌体 circRNA 的差异上调。我们的研究强调了介导格雷夫斯病免疫激活的多种途径，特别是病毒感染和干扰素-β信号传导。
Background 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. Methods 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. Results 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. Conclusions 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.