A Preliminary Exploration Of Circulating Micrornas As Potential Biomarkers Of Systemic Lupus Erythematosus

Objects: To investigate the aberrant expression of circulating microRNAs (miRNAs) in patientswith systemic lupus erythematosus (SLE).Methods: In this study, a miRNA profile was used to determine the aberrantly expressedcirculating miRNAs in patients with systemic lupus erythematosus (n=10) compared withpatients with rheumatoid arthritis (RA)(n=10) and healthy controls (n=10). To further confirmthe microarray data, we identified8miRNAs (miR-126, miR-21, miR-451, miR-223, miR-16,miR-125a-3p, miR-155, and miR-146a) by real-time quantitative PCR (qRT-PCR) in20healthycontrols and in55patients, of whom30patients were diagnosed with SLE and25werediagnosed with RA. In addition, to further estimate the potential roles of these differentiallyexpressed circulating miRNAs in the pathogenesis of SLE, we utilized a bioinformaticsexploratory analysis.Results: A total of51miRNAs were significantly differentially expressed when comparing theSLE patients to the healthy controls, with32circulating miRNAs downregulated and19upregulated. There were40miRNAs (22downregulated and18upregulated) that weresignificantly different in the RA samples versus the healthy controls. Remarkably, there weremultiple overlaps between the differentially expressed circulating miRNAs identified in the SLEsamples versus the healthy controls and those from the RA samples versus the healthy controls.Of the51differentially expressed circulating miRNAs identified in the SLE samples,35werealso found among the40RA-derived circulating miRNAs. Interestingly, DNAmethylation-associated miR-126a is specifically upregulated in the patients with SLE comparedto both the healthy controls and to the RA patients, whereas it is significantly downregulated inthe RA patients, indicating that miR-126may be attractive candidate as a potential biomarker ofSLE. In addition to miR-126, four other miRNAs (miR-21, miR-16, miR-451, and miR-223) hadincreased levels in the SLE patients; however, miR-21, miR-16, miR-223, and miR-451werealso upregulated in the RA patients to the same level as in the SLE patients, indicating thatmiR-126may be attractive candidate as a potential biomarker of SLE. In this assay thecirculating levels of inflammation associated miR-125a-3p and miR-155a and SLE-associated miR-146a were significantly downregulated in patients. The bioinformatics exploratory analysisidentified a number of significantly enriched pathways, which implied that most dysregulatedcirculating miRNAs might be involved in various signal transduction pathways and cellinteractions, particularly the MAPK signaling pathway.Conclusion: Based on these findings, we postulate that aberrantly expressed plasma miRNAscould be attractive as candidates for putative biomarkers of SLE and may help elucidate thepossible pathogenesis of SLE.