Circulating microRNAs as Potential Diagnostic Biomarkers for Poor Sleep Quality

Purpose: Persistent poor sleep quality leads to impaired cognitive performance and an inability to perform daily activities. Biomarker-assisted diagnosis is important for the early treatment of poor sleep quality; however, diagnostic biomarkers for poor sleep quality remain unidentified. Circulating microRNAs (miRNAs) have been reported to be linked to the pathogenesis of poor sleep quality, indicating their possible role in sleep problem diagnosis. The present study aimed to identify potential miRNA biomarkers for poor sleep quality.

Patients and methods: Differentially expressed serum miRNAs in patients with poor sleep quality and healthy controls (n=20) were analyzed via small RNA sequencing. Two-step quantitative RT-PCR in the two independent populations and receiver operating characteristic (ROC) analyses were used to validate the identified miRNAs. In silico analysis was then used to identify the target genes.

Results: Of the 59 circulating miRNAs identified via differential analysis, six were validated for differential expression by quantitative RT-PCR (n=60). Two of these six miRNAs, miR-4433b-3p and miR-619-5p, were reconfirmed in the second validation with an independent validation cohort (n=59). ROC analyses (n=40) revealed the probability of the two miRNAs as potential biomarkers with areas under the ROC curve (AUCs) of 0.81 and 0.70, respectively. The combined AUC was 0.86, which was much higher than that of each miRNA. Using in silico target gene analysis, the target genes of the two miRNAs were identified to be associated with the regulation of the circadian rhythm and inflammatory pathways.

Conclusion: Our results revealed that miR-619-5p and miR-4433b-3p could be developed as potential diagnostic biomarkers for poor sleep quality. The combination of both miRNAs may be more effective than the use of the individual miRNA for sleep problem diagnosis.