Circulating microRNA molecular signatures converge with erythroid phenotypes and iron homeostasis in pediatric tic...

Tic disorders (TDs) are common neurodevelopmental conditions with unclear pathogenesis and a lack of objective biomarkers. This study aimed to explore the associations among circulating microRNAs (miRNAs), erythroid phenotypes, iron homeostasis, and pediatric TD.

A total of 30 TD children and 10 healthy controls were enrolled. Serum levels of five candidate miRNAs, erythroid parameters, and iron metabolism indicators were detected. In this study, serum levels of five candidate miRNAs were quantified in children with tic disorders and age- and sex-matched normal controls using RT-qPCR. Erythroid phenotypes and serum iron-metabolism indicators were assessed in parallel. Differential expression analyses, multivariate modeling, and network-based target and functional enrichment analyses were performed to explore integrated molecular signatures.

Results showed that hsa-miR-125b-5p and hsa-miR-23a-3p were significantly upregulated in the TD group. TD children exhibited lower hemoglobin, mean corpuscular volume (MCV), serum ferritin, transferrin (TrF), total ironbinding capacity, and soluble transferrin receptor, along with higher mean corpuscular hemoglobin concentration, while hemoglobin fractions remained unchanged. The integrated model combining hsa-miR-125b-5p, MCV, and TrF showed excellent diagnostic performance (AUC=0.977). Network and enrichment analyses revealed convergent biological pathways involving cellular and multicellular homeostasis, metal ion regulation, and TGF-β/BMP-associated signaling, linking miRNA-associated regulatory networks to erythroid and ironrelated processes.

In conclusion, children with TD may exhibit homeostatic dysregulation of circulating miRNAs, erythroid profiles, and iron metabolism. This integrative molecular framework may provide insight into peripheral regulatory mechanisms relevant to neurodevelopmental pathology.