Genome-wide, integrative analysis implicates exosome-derived microRNA dysregulation in chronic insomnia.

Study objectives: Insomnia, characterized by difficulty in initiating and sustaining sleep or waking prematurely without the ability to return to sleep, affects approximately 30% of the population. The underlying mechanisms of insomnia remain unclear, and the objective diagnostic measures are scarce. It is an opportunity to explore the roles of peripheral blood exosomal miRNAs in insomnia patients.

Methods: Exosomal miRNAs were isolated from 20 insomnia patients and an equal number of healthy individuals. A comprehensive genome-wide miRNA expression analysis was conducted to identify differential miRNAs between the two groups. To evaluate the diagnostic potential of these miRNAs, receiver-operating characteristic (ROC) curves were employed. Furthermore, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the target genes of differential exosome miRNA to explore their regulated signaling pathways and molecular functions.

Results: We identified 51 differentially expressed miRNAs. Among these, miR-182-5p and miR-451a were markedly downregulated in patients as evidenced by their area-under-the-curve values. The areas under the ROC curves and 95% confidence intervals (CIs) of miR-182-5p and miR-451a in predicting the possibility of chronic insomnia patients were 0.863 (95% CI = 0.75 to 0.97) and 0.813 (95% CI = 0.68 to 0.95). Coexpression network analysis and enrichment analysis of miRNA target genes shed light on the molecular pathophysiology of insomnia, including autophagy and mitophagy.

Conclusions: These findings suggest that peripheral blood exosomal miRNAs may serve as potential noninvasive biomarkers for insomnia diagnosis and provide new insights into the molecular mechanisms underlying this sleep disorder.