Abstract
Background
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.
Methods and Results
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.
Conclusion
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.
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Funding
This work was supported by the grants from the National Natural Science Foundation of China (81671642 and 81870651), Tianjin Science and Technology Support Plan (20YFZCSY00990), Natural Science Foundation of Tianjin (20JCZDJC00100), Tianjin Key Medical Discipline (Specialty) Construction Project, the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2019ZD030), Tianjin Key Laboratory of Retinal Functions and Diseases (2019tjswmq004), and Tianjin Medical University Eye Hospital (TJLCZDXKQ006).
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Xiaomin Zhang conceived the study. Kailei Guo wrote the paper, Baiyi Li and Mi Zhang did the experiments, Fuhua Yang and Guixia Zhao revised the manuscript. All authors read and approved the final manuscript. And the authors thank Xinyi Zhang for guidance and assistance in sample collection.
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The study was approved by the Local Ethics Research Committee of Tianjin Medical University Eye Hospital (No. 2016KY-14).
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Kailei Guo, Baiyi Li, and Fuhua Yang contributed equally to this manuscript.
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Guo, K., Li, B., Yang, F. et al. Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt–Koyanagi–Harada Disease. Mol Biol Rep 49, 11421–11431 (2022). https://doi.org/10.1007/s11033-022-07753-y
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DOI: https://doi.org/10.1007/s11033-022-07753-y