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

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 DESeq۲ 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-۹۳-۵p functions as the primary high-connectivity hub microRNA, interacting with one hundred and ninety-five high-confidence targets. Furthermore, the gene ATXN۱ 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-۱ signaling, and adenosine monophosphate-activated protein kinase signaling were significantly enriched. This study highlights a novel, systematic regulatory axis involving hsa-miR-۹۳-۵p and ATXN۱ 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.

کلیدواژه ها:

MicroRNA ، Eczema ، hsa-miR-۹۳-۵p ، ATXN۱ ، Systematic network analysis