Correlation of potential diagnostic biomarkers (circulating miRNA and protein) of bipolar II disorder

Objectives: We previously identified certain peripheral biomarkers of bipolar II disorder (BD-II) including circulating miRNAs (miR-7-5p, miR-142–3p, miR-221–5p, and miR-370–3p) and proteins (Matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)). We try to explore the connection between these biomarkers. Methods: We explored correlations between the peripheral levels of above circulating miRNAs and proteins in our previously collected BD-II (N = 96) patients and control (N = 115) groups. We further searched TargetScan and BioGrid websites to identify direct and indirect interactions between these protein-coding genes and circulating miRNAs. Results: In the BD-II group, we identified significant correlations between the miR-221–5p and CA-1 (rho = −0.323, P = 0.001), FARSB (rho = 0.251, P = 0.014), MMP-9 (rho = 0.313, P = 0.002) and PCSK9 (rho = 0.252, P = 0.014). The miR-370–3p also significantly correlated with FARSB expression (rho = 0.330, P = 0.001) and PCSK9 expression (rho = 0.221, P = 0.031) in the BD-II group. Our findings were in line with the modulating axis identified from TargetScan and BioGrid, miR-221–5p/CA-1/MMP9 and miR-370–3p/FARSB/PCSK9, suggesting their association with BD-II. Conclusion: Our result supported that peripheral candidate miRNA and protein biomarkers may interact in BD-II. We concluded that miR-221–5p/CA-1/MMP9 and miR-370–3p/FARSB/PCSK9 axes might act a critical role in the pathomechanism of BD-II.