Guo Kailei, Li Baiyi, Yang Fuhua, Zhang Mi, Zhao Guixia, Zhang Xiaomin
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute, School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Tangshan Eye Hospital, Tangshan, China.
Mol Biol Rep. 2022 Dec;49(12):11421-11431. doi: 10.1007/s11033-022-07753-y. Epub 2022 Aug 21.
Vogt-Koyanagi-Harada (VKH) disease is a common type of uveitis that leads to blindness. The clinical manifestations and treatment solutions are different between initial-onset and recurrent VKH. Therefore, identifying the microRNA (miRNA) profiles from initial-onset and recurrent VKH patients may shed light on the molecular mechanisms underlying the pathogenesis of VKH disease.
RNAs isolated from peripheral blood mononuclear cells (PBMCs) from patients with initial-onset VKH, recurrent VKH, and healthy individuals were subjected to high-throughput miRNA sequencing. Pairwise analysis of miRNA sequencing data between groups was conducted to identify differentially expressed miRNAs (DEMs), which were verified using real-time quantitative polymerase chain reaction. After receiver operating characteristic analyses, we found that hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers of different VKH stages. DEMs were classified into three groups based on their differential expression: DEMs in initial-onset stage, DEMs in recurrent stage, and DEMs common between both VKH stages (shared DEMs). Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes identified the mitogen-activated protein kinase, tumor necrosis factor, and mechanistic target of rapamycin kinase pathways as significantly enriched among the target genes of recurrent stage and shared DEMs. Furthermore, we mapped a network of competing endogenous RNAs for hsa-miR-206, which we used to identify putative targets for VKH treatment.
Hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers for different stages of VKH. Additionally, our competing endogenous RNA network of hsa-miR-206 provides a new direction for VKH treatment.
伏格特-小柳-原田(VKH)病是一种常见的葡萄膜炎类型,可导致失明。初发性和复发性VKH的临床表现及治疗方案有所不同。因此,鉴定初发性和复发性VKH患者的微小RNA(miRNA)谱可能有助于揭示VKH病发病机制的分子机制。
从初发性VKH患者、复发性VKH患者和健康个体的外周血单个核细胞(PBMC)中分离出的RNA进行高通量miRNA测序。对各组间的miRNA测序数据进行成对分析,以鉴定差异表达的miRNA(DEM),并通过实时定量聚合酶链反应进行验证。经过受试者工作特征分析,我们发现hsa-miR-4664-3p、hsa-miR-7704、hsa-miR-4504和hsa-miR-206可能作为不同VKH阶段的生物标志物。根据差异表达情况,将DEM分为三组:初发性阶段的DEM、复发性阶段的DEM以及两个VKH阶段共有的DEM(共享DEM)。使用京都基因与基因组百科全书进行通路富集分析,结果显示丝裂原活化蛋白激酶、肿瘤坏死因子和雷帕霉素激酶机制靶点通路在复发性阶段和共享DEM的靶基因中显著富集。此外,我们绘制了hsa-miR-206的竞争性内源RNA网络,用于确定VKH治疗的潜在靶点。
hsa-miR-4664-3p、hsa-miR-7704、hsa-miR-4504和hsa-miR-206可能作为VKH不同阶段的生物标志物。此外,我们构建的hsa-miR-206竞争性内源RNA网络为VKH治疗提供了新方向。