Department of Clinical Laboratory Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cell Biol Int. 2022 Apr;46(4):649-659. doi: 10.1002/cbin.11760. Epub 2022 Jan 23.
Exosomes are being extensively studied as a source of valuable new biomarkers. The underlying mechanism of ankylosing spondylitis (AS) may include changes in the circular RNAs (circRNAs) of exosomes. However, there is a lack of reports on the role of exosomal cirRNAs in the plasma of patients with AS. We isolated exosomes from the plasma of patients with AS and healthy individuals (controls). Subsequently, we investigated the circRNA profiles of the exosomes via high-throughput RNA sequencing and identified 56 differentially expressed circRNAs in the exosomes of patients with AS compared with those of the healthy controls. Gene Ontology demonstrated that the differentially expressed circRNAs were mainly involved in the negative regulation of the activity of the transcription factor nuclear factor-κB and bone remodelling that is potentially related to AS. Kyoto Encyclopedia Genes and Genome demonstrated that the most highly AS-correlated pathways that were identified were 'notch signalling pathway' and those primarily involved with 'cholinergic synapse'. Finally, we validated five differentially expressed circRNAs using quantitative real-time polymerase chain reaction and predicted their potential functions through the circRNA-miRNA-mRNA network. Our study is the first to report changes in exosomal circRNAs from plasma samples of patients with AS, and provide novel targets for further investigation of molecular mechanisms and potential intervention therapy targets of AS.
外泌体作为有价值的新型生物标志物的来源正在被广泛研究。强直性脊柱炎（AS）的潜在机制可能包括外泌体环状 RNA（circRNA）的变化。然而，关于 AS 患者血浆中外泌体 cirRNA 的作用的报道较少。我们从 AS 患者和健康个体（对照）的血浆中分离出外泌体。随后，我们通过高通量 RNA 测序研究了外泌体的 circRNA 图谱，发现与健康对照组相比，AS 患者外泌体中有 56 个差异表达的 circRNA。基因本体论表明，差异表达的 circRNA 主要参与核因子-κB 转录因子活性和骨重塑的负调控，这可能与 AS 有关。京都基因与基因组百科全书表明，鉴定出的与 AS 相关性最高的途径是“Notch 信号通路”和主要涉及“胆碱能突触”的途径。最后，我们使用定量实时聚合酶链反应验证了五个差异表达的 circRNA，并通过 circRNA-miRNA-mRNA 网络预测了它们的潜在功能。我们的研究首次报道了 AS 患者血浆中外泌体 circRNA 的变化，并为进一步研究 AS 的分子机制和潜在干预治疗靶点提供了新的靶标。
