The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.
Front Immunol. 2021 Dec 22;12:738760. doi: 10.3389/fimmu.2021.738760. eCollection 2021.
Recent studies revealed that circular RNAs (circRNAs) are important in numerous biological process and involved in autoimmune diseases. However, their role in Vogt-Koyanagi-Harada (VKH) disease, a classical autoimmune disease, is not yet known. This research aimed to study the expression profile of mRNAs, microRNAs (miRNAs) and circRNAs and investigate the influence of circRNAs on the pathogenesis of VKH disease. We identified circRNAs, miRNAs, and mRNAs expression profiles in CD4 T cells between 4 VKH patients and 3 healthy controls using the whole-transcriptome sequencing (RNA-seq) technique. We discovered that a total of 5088 mRNAs, 451 circRNAs and 433 miRNAs were differently expressed. The GO and KEGG pathway enrichment analyses were performed for significantly differentially expressed circRNAs and mRNAs. GSEA was conducted for all mRNAs. The functional enrichment suggested that the inflammatory response, the adaptive immune response, NF-kappa B signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation and T cell receptor signaling pathway were associated with VKH disease. In addition, based on the immune-related genes we screened, the circRNA-miRNA-mRNA ceRNA network was analyzed and constructed. Ten differently expressed mRNAs (LAT, ZAP70, ITK, ICOS, RASGRP1, PAG1, PLCG1, PRKCQ, LCK, CARD11) and 5 differently expressed circRNAs (hsa_circ_0033144, hsa_circ_0000233, hsa_circ_0000396, hsa_circ_0001924, hsa_circ_0001320) were selected to be validated by Real-time qPCR (RT-qPCR). The results of RT-qPCR turned out to be consistent with RNA-seq data. Further analysis showed that hsa_circ_0001320 and hsa_circ_0001924 may serve as crucial candidate marker genes of VKH disease. These results reveal that circRNAs may have a crucial immunomodulatory function in the pathophysiological process of VKH disease.
最近的研究表明，环状 RNA（circRNAs）在许多生物过程中具有重要作用，并参与自身免疫性疾病。然而，它们在 Vogt-Koyanagi-Harada（VKH）病中的作用尚不清楚，VKH 病是一种经典的自身免疫性疾病。本研究旨在研究信使 RNA（mRNA）、微小 RNA（miRNA）和环状 RNA 的表达谱，并探讨环状 RNA 对 VKH 病发病机制的影响。我们使用全转录组测序（RNA-seq）技术在 4 名 VKH 患者和 3 名健康对照者的 CD4 T 细胞中鉴定出 circRNAs、miRNAs 和 mRNAs 的表达谱。我们发现，总共 5088 个 mRNA、451 个 circRNA 和 433 个 miRNA 表达水平存在差异。对显著差异表达的 circRNAs 和 mRNAs 进行了 GO 和 KEGG 通路富集分析。对所有 mRNAs 进行了 GSEA 分析。功能富集表明，VKH 病与炎症反应、适应性免疫反应、NF-kappa B 信号通路、Th17 细胞分化、Th1 和 Th2 细胞分化以及 T 细胞受体信号通路有关。此外，基于我们筛选出的免疫相关基因，分析并构建了 circRNA-miRNA-mRNA ceRNA 网络。选择了 10 个差异表达的 mRNA（LAT、ZAP70、ITK、ICOS、RASGRP1、PAG1、PLCG1、PRKCQ、LCK、CARD11）和 5 个差异表达的 circRNA（hsa_circ_0033144、hsa_circ_0000233、hsa_circ_0000396、hsa_circ_0001924、hsa_circ_0001320）通过实时 qPCR（RT-qPCR）进行验证。RT-qPCR 的结果与 RNA-seq 数据一致。进一步分析表明，hsa_circ_0001320 和 hsa_circ_0001924 可能作为 VKH 病的关键候选标记基因。这些结果表明，circRNAs 可能在 VKH 病的病理生理过程中具有重要的免疫调节功能。
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