Department of Rheumatology and Immunology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Nan Li Shi Road No. 56, Beijing, 100045, China.
Clin Rheumatol. 2019 May;38(5):1339-1350. doi: 10.1007/s10067-018-4392-8. Epub 2019 Jan 9.
Recently, it was reported that circular RNAs (circRNAs) play the crucial role in many physiological and biological processes and can be used as biomarkers. However, the information about circRNAs in children with systemic lupus erythematosus (SLE) is limited. The aim of this study is to determine the expression of circRNAs in children with SLE and investigate the significance of circRNA for diagnosing SLE.
Microarray profile of circRNAs and mRNAs was performed for identifying the changes in expression of circRNAs and mRNAs between children with SLE and healthy children. Quantitative polymerase chain reaction (qPCR) was used to confirm the results. Spearman correlation test was performed to assess the correlation between circRNAs and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value.
A comparison between the children with SLE and healthy children revealed that 348 circRNAs and 1162 mRNAs were expressed differentially. The authors constructed a complex circRNA target network consisting of 307 matched circRNA-mRNA pairs for 124 differentially expressed circRNAs (74 circRNAs were upregulated, and 50 circRNAs were downregulated) and 142 differentially expressed mRNAs (83 mRNAs were upregulated, and 59 mRNAs were downregulated) by using gene co-expression network analysis. The competing for endogenous RNA (ceRNA) network includes 42 differentially expressed circRNAs, 41 differentially expressed mRNAs, and 71 predicted miRNAs. Among these SLE patients, we detected that the hsa_circ_0021372 and hsa_circ_0075699 levels are associated with C3 and C4 levels in children with SLE. The hsa_circ_0057762 level is positively associated with the SLEDAI-2K score. The ROC curves of circRNAs showed that the levels of hsa_circ_0057762 (AUC 0.804, 95% CI 0.607-1.0, P = 0.02) and hsa_circ_0003090 (AUC 0.848, 95% CI 0.688-1.0, P = 0.008) could differentiate the patients with SLE from the healthy controls.
We firstly characterized the expression profiles of circRNA and mRNA in children with SLE and propose herein their possible roles in the pathogenesis of SLE. These results provide novel insight into the mechanisms of SLE pathogenesis, and circRNAs may serve as useful biomarkers for SLE.
最近有报道称，环状 RNA（circRNAs）在许多生理和生物过程中发挥着关键作用，并可用作生物标志物。然而，关于儿童系统性红斑狼疮（SLE）中 circRNAs 的信息有限。本研究旨在确定 SLE 患儿中 circRNAs 的表达情况，并探讨 circRNA 对诊断 SLE 的意义。
通过微阵列分析 circRNAs 和 mRNAs 的表达谱，以鉴定 SLE 患儿与健康儿童之间 circRNAs 和 mRNAs 表达的变化。采用实时定量聚合酶链反应（qPCR）验证结果。采用 Spearman 相关检验评估 circRNAs 与临床变量之间的相关性。绘制受试者工作特征（ROC）曲线评估诊断价值。
SLE 患儿与健康儿童的比较显示，有 348 个 circRNAs 和 1162 个 mRNAs 表达差异。作者通过基因共表达网络分析构建了一个包含 307 个匹配的 circRNA-mRNA 对的复杂 circRNA 靶标网络，用于 124 个差异表达的 circRNAs（74 个 circRNAs 上调，50 个 circRNAs 下调）和 142 个差异表达的 mRNAs（83 个 mRNAs 上调，59 个 mRNAs 下调）。竞争性内源性 RNA（ceRNA）网络包括 42 个差异表达的 circRNAs、41 个差异表达的 mRNAs 和 71 个预测的 miRNA。在这些 SLE 患者中，我们检测到 hsa_circ_0021372 和 hsa_circ_0075699 的水平与 SLE 患儿的 C3 和 C4 水平相关。hsa_circ_0057762 水平与 SLEDAI-2K 评分呈正相关。circRNAs 的 ROC 曲线显示，hsa_circ_0057762（AUC 0.804，95%CI 0.607-1.0，P=0.02）和 hsa_circ_0003090（AUC 0.848，95%CI 0.688-1.0，P=0.008）的水平可区分 SLE 患者与健康对照组。
我们首次描述了儿童 SLE 中 circRNA 和 mRNA 的表达谱，并提出了它们在 SLE 发病机制中的可能作用。这些结果为 SLE 发病机制提供了新的见解，circRNAs 可能作为 SLE 的有用生物标志物。
