Integrated Bioinformatic Analysis of Plasma microRNA Sequencing Profiles Identifies a Potential Regulatory Network in Atopic Dermatitis

Document Type : Research Article

Author

Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

10.22080/jgr.2026.31328.1458

Abstract

Atopic dermatitis is a prevalent, chronic inflammatory skin disorder characterized by complex interactions between epidermal barrier dysfunction and immune system dysregulation. Although microRNAs have emerged as crucial post-transcriptional regulators of gene expression, their specific systemic profiles and overarching regulatory networks in human plasma remain insufficiently characterized. This study aims to provide a comprehensive, network-level understanding of microRNA-mediated regulation in atopic dermatitis to identify central molecular drivers and potential therapeutic targets. We conducted a systematic re-analysis of plasma microRNA sequencing data from patients with atopic dermatitis and healthy controls. The computational workflow utilized the Galaxy platform and the DESeq2 algorithm for differential expression analysis, incorporating rigorous statistical pre-filtering to ensure data quality. High-confidence target genes were predicted through a triple-consensus approach integrating multiple specialized databases. A comprehensive microRNA-target interaction network was then constructed, followed by topological analysis to identify influential regulatory hubs and biological pathway enrichment. Our analysis identified twenty-six differentially expressed miRNAs, comprising seventeen down-regulated and nine up-regulated molecules. Topological analysis revealed that hsa-miR-93-5p functions as the primary high-connectivity hub microRNA, interacting with one hundred and ninety-five high-confidence targets. Furthermore, the gene ATXN1 was identified as a central hub within the messenger RNA network. Functional enrichment analysis demonstrated that these targets are primarily involved in enzyme-linked receptor signaling pathways and, additionally, pathways related to metabolic stress, hypoxia-inducible factor-1 signaling, and adenosine monophosphate-activated protein kinase signaling were significantly enriched. This study highlights a novel, systematic regulatory axis involving hsa-miR-93-5p and ATXN1 in the pathogenesis of atopic dermatitis. By shifting the focus from single-pair interactions to a global network perspective, these findings provide a robust framework for identifying biomarkers and developing multi-target therapeutic strategies aimed at restoring skin barrier homeostasis and modulating cutaneous inflammation. While these computational insights offer high-confidence candidates, further experimental validation is essential to confirm their clinical utility.

Keywords

Main Subjects


Afshari, M., Kolackova, M., Rosecka, M., Celakovská, J., & Krejsek, J. (2024). Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches. Frontiers in Immunology, 15. https://doi.org/10.3389/fimmu.2024.1361005
Bakker, D., de Bruin-Weller, M., Drylewicz, J., van Wijk, F., & Thijs, J. (2023). Biomarkers in atopic dermatitis. Journal of Allergy and Clinical Immunology, 151(5), 1163-1168. https://doi.org/10.1016/j.jaci.2023.01.019
Buijsen, R. A. M., Hu, M., Saez‐González, M., Notopoulou, S., Mina, E., Koning, W., Gardiner, S. L., van der Graaf, L. M., Daoutsali, E., Pepers, B. A., Mei, H., van Dis, V., Frimat, J., van den Maagdenberg, A. M. J. M., Petrakis, S., & van Roon‐Mom, W. M. C. (2023). Spinocerebellar ataxia type 1 characteristics in patient‐derived fibroblast and iPSC-derived neuronal cultures. Movement Disorders, 38(8), 1428-1442. https://doi.org/10.1002/mds.29446
Carreras-Badosa, G., Maslovskaja, J., Vaher, H., Pajusaar, L., Annilo, T., Lättekivi, F., Hübenthal, M., Rodriguez, E., Weidinger, S., Kingo, K., & Rebane, A. (2022). miRNA expression profiles of the perilesional skin of atopic dermatitis and psoriasis patients are highly similar. Scientific Reports, 12(1), 22645. https://doi.org/10.1038/s41598-022-27235-2
Criado, P. R., Miot, H. A., Bueno-Filho, R., Ianhez, M., Criado, R. F. J., & de Castro, C. C. S. (2024). Update on the pathogenesis of atopic dermatitis. Anais Brasileiros de Dermatologia, 99(6), 895-915. https://doi.org/10.1016/j.abd.2024.06.001
Didonna, A., Canto Puig, E., Ma, Q., Matsunaga, A., Ho, B., Caillier, S. J., Shams, H., Lee, N., Hauser, S. L., Tan, Q., Zamvil, S. S., & Oksenberg, J. R. (2020). Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis. Proceedings of the National Academy of Sciences, 117(38), 23742-23750. https://doi.org/10.1073/pnas.2003798117
Facheris, P., Jeffery, J., Del Duca, E., & Guttman-Yassky, E. (2023). The translational revolution in atopic dermatitis: the paradigm shifts from pathogenesis to treatment. Cellular and Molecular Immunology, 20(5), 448-474. https://doi.org/10.1038/s41423-023-00992-4
Gao, S., Chen, T., Hao, Y., Zhang, F., Tang, X., Wang, D., Wei, Z., & Qi, J. (2020). Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression. Stem Cell Research and Therapy, 11(1), 56. https://doi.org/10.1186/s13287-020-1570-9
He, K., Zang, J., Ren, T., Feng, S., Liu, M., Zhang, X., Sun, W., Chu, J., Xu, D., & Liu, F. (2024). Therapeutic potential and mechanisms of mesenchymal stem cell and mesenchymal stem cell-derived extracellular vesicles in atopic dermatitis. Journal of Inflammation Research, 17, 5783-5800. https://doi.org/10.2147/JIR.S479444
Hou, T., Sun, X., Zhu, J., Hon, K.-L., Jiang, P., Chu, I. M.-T., Tsang, M. S.-M., Lam, C. W.-K., Zeng, H., & Wong, C.-K. (2020). IL-37 ameliorating allergic inflammation in atopic dermatitis through regulating microbiota and AMPK-mTOR signaling pathway-modulated autophagy mechanism. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.00752
Kalantari-Dehaghi, M., Ghohabi-Esfahani, N., & Emadi-Baygi, M. (2025). From bulk RNA sequencing to spatial transcriptomics: a comparative review of differential gene expression analysis methods. Human Genomics, 20(1), 9. https://doi.org/10.1186/s40246-025-00884-w
Khosrojerdi, M., Azad, F. J., Yadegari, Y., Ahanchian, H., & Azimian, A. (2024). The role of microRNAs in atopic dermatitis. Non-Coding RNA Research, 9(4), 1033-1039. https://doi.org/10.1016/j.ncrna.2024.05.012
Kim, J., Kim, B. E., & Leung, D. Y. M. (2019). Pathophysiology of atopic dermatitis: Clinical implications. Allergy and Asthma Proceedings, 40(2), 84-92. https://doi.org/10.2500/aap.2019.40.4202
Lee, S. E., Jeong, S. K., & Lee, S. H. (2010). Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis. Yonsei Medical Journal, 51(6), 808-822. https://doi.org/10.3349/ymj.2010.51.6.808
Meng, L., Li, M., Gao, Z., Ren, H., Chen, J., Liu, X., Cai, Q., Jiang, L., Ren, X., Yu, Q., Chen, J., & Yang, L. (2019). Possible role of hsa-miR-194-5p, via regulation of HS3ST2, in the pathogenesis of atopic dermatitis in children. European Journal of Dermatology, 29(6), 603-613. https://doi.org/10.1684/ejd.2019.3676
Na, K. S., Park, J., Kim, S. M., Lee, J., Lee, E., Woo, W., Choi, J., Kim, L. K., & Park, K. M. (2026). Engineered atopic dermatitis models for recreating hypoxic conditions in atopic dermatitis microenvironments. Bioactive Materials, 59, 512-534. https://doi.org/10.1016/j.bioactmat.2025.12.045
Nishimoto, R., Kodama, C., Yamashita, H., & Hattori, F. (2023). Human induced pluripotent stem cell-derived keratinocyte-like cells for research on protease-activated receptor 2 in nonhistaminergic cascades of atopic dermatitis. The Journal of Pharmacology and Experimental Therapeutics, 384(2), 248-253. https://doi.org/10.1124/jpet.122.001412
Peng, S., Chen, M., Yin, M., & Feng, H. (2021). Identifying the potential therapeutic targets for atopic dermatitis through the immune infiltration analysis and construction of a ceRNA network. Clinical, Cosmetic and Investigational Dermatology, 14, 437-453. https://doi.org/10.2147/CCID.S310426
Sindhu, B. S., Adiga, U. S., Kumar, K. P., Sindhuja, N., Ravikanth, E. V., & Sneha, K. H. (2025). Genetic and molecular characterization of atopic eczema: A comprehensive bioinformatics analysis of gene interactions and pathways. Biomedical and Biotechnology Research Journal, 9(2), 208-215. https://doi.org/10.4103/bbrj.bbrj-101-25
Song, J., Kim, D., Lee, S., Jung, J., Joo, J. W. J., & Jang, W. (2022). Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning. Communications Biology, 5(1), 615. https://doi.org/10.1038/s42003-022-03564-w
Sroka-Tomaszewska, J., & Trzeciak, M. (2021). molecular mechanisms of atopic dermatitis pathogenesis. International Journal of Molecular Sciences, 22(8), 4130. https://doi.org/10.3390/ijms22084130
Szilveszter, K. P., Németh, T., & Mocsai, A. (2019). Tyrosine kinases in autoimmune and inflammatory skin diseases. Frontiers in Immunology, 10, 1862 https://doi.org/10.3389/fimmu.2019.01862
Vagiona, A.-C., Andrade-Navarro, M. A., Psomopoulos, F., & Petrakis, S. (2020). Dynamics of a protein interaction network associated to the aggregation of polyQ-expanded Ataxin-1. Genes, 11(10), 1129. https://doi.org/10.3390/genes11101129
Wan, J., Shin, D. B., & Syed, M. N. (2022). 31772 Malignancy risk among children and adults with atopic dermatitis in a population-based cohort. Journal of the American Academy of Dermatology, 87(3), AB79. https://doi.org/10.1016/j.jaad.2022.06.350
Wan, J., Shin, D. B., Syed, M. N., Abuabara, K., Lemeshow, A. R., Fuxench, Z. C. C., & Gelfand, J. M. (2023). Malignancy risk in patients with atopic dermatitis: a population-based cohort study. British Journal of Dermatology, 189(1), 53-61. https://doi.org/10.1093/bjd/ljad072
Weare-Regales, N., Chiarella, S. E., Cardet, J. C., Prakash, Y. S., & Lockey, R. F. (2022). Hormonal effects on asthma, rhinitis, and eczema. The Journal of Allergy and Clinical Immunology: In Practice, 10(8), 2066-2073. https://doi.org/10.1016/j.jaip.2022.04.002
Weihrauch, T., Limberg, M. M., Gray, N., Schmelz, M., & Raap, U. (2023). Neurotrophins: Neuroimmune interactions in human atopic diseases. International Journal of Molecular Sciences, 24(7), 6105. https://doi.org/10.3390/ijms24076105
Wollenberg, A., Werfel, T., Ring, J., Ott, H., Gieler, U., & Weidinger, S. (2023). Atopic dermatitis in children and adults: diagnosis and treatment. Deutsches Arzteblatt International, 120(13), 224-234.‏ https://doi.org/10.3238/arztebl.m2023.001
Wu, P., Cao, Y., Zhao, R., & Wang, Y. (2019). miR‐96‐5p regulates wound healing by targeting BNIP3/FAK pathway. Journal of Cellular Biochemistry, 120(8), 12904-12911. https://doi.org/10.1002/jcb.28561
Zhang, N., Zhong, Z., Wang, Y., Yang, L., Wu, F., Peng, C., Huang, W., & He, G. (2019). Competing endogenous network analysis identifies lncRNA Meg3 activates inflammatory damage in UVB induced murine skin lesion by sponging miR-93-5p/epiregulin axis. Aging, 11(22), 10664-10683. https://doi.org/10.18632/aging.102483
Zhu, H., She, Q., Li, H., Zhang, N., Huang, W., Xu, Y., Liu, Z., & Liang, Y. (2025). EGFR-TKIs induce acneiform rash and xerosis via Caspase-3/GSDME-mediated pyroptosis of keratinocytes and sebocytes. Toxicology, 511, 154018. https://doi.org/10.1016/j.tox.2024.154018
Zhu, Y., Wang, H., He, J., Yang, L., Zhou, X., Li, Z., Zhou, H., Zhao, H., & Li, Y. (2022). Atopic dermatitis and skin cancer risk: A systematic review. Dermatology and Therapy, 12(5), 1167-1179. https://doi.org/10.1007/s13555-022-00720-2