Expression and clinical significance of circular RNAs hsa_circ_0000175 and hsa_circ_0008410 in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Abstract

circular RNAs (circRNAs) are a novel class of RNAs that may be used as biomarkers in clinical blood samples. However, the role of circRNAs in rheumatoid arthritis (RA) has not been extensively investigated. In the present study, six circRNAs, including hsa_circ_0082689, hsa_circ_0087798, hsa_circ_0000175, hsa_circ_0008410, hsa_circ_0049356 and hsa_circ_0032959 levels were determined in peripheral blood mononuclear cells (PBMcs) collected from 24 patients with RA and 24 healthy controls (Hc) by reverse transcription-quantitative polymerase chain reaction (RT-qPcR) analysis. Hsa_circ_0000175 and hsa_circ_0008410 were selected for further evaluation in an independent cohort consisting of 63 patients with RA, 50 with systemic lupus erythematosus (SLE), 24 with ankylosing spondylitis (AS) and 21 Hc. Spearman's rank correlation coefficient was used to analyze the correlation between these two circRNAs and the clinical characteristics of RA, and receiver operating characteristic (ROc) curves were constructed to evaluate their value in RA diagnosis. Multivariate analysis (logistic regression) was used to analyze the risk factors. Of the six selected circRNAs, the expression of hsa_circ_0000175 was found to be significantly reduced and the expression of hsa_circ_0008410 was significantly elevated in PBMCs from patients with RA compared with their levels in Hc. The expression of hsa_circ_0000175 in patients with RA was correlated with anti-citrullinated protein antibodies, white blood cell count, lymphocyte count, lymphocyte percentage, neutrophil count, neutrophil percentage and neutrophil-to-lymphocyte ratio. Furthermore, the expression of hsa_circ_0008410 was correlated with tender joint count, disease duration, platelet count and plateletcrit, indicating the activity and severity of RA. ROc curve analysis suggested that hsa_circ_0000175, hsa_circ_0008410, and the combination of hsa_circ_0000175 and hsa_circ_0008410 have significant value in the diagnosis of RA. Hsa_circ_0000175 and hsa_circ_0008410 also differed significantly between patients with RA, and those with SLE and AS. Moreover, logistic regression analysis revealed that the expression of PBMc hsa_circ_0000175 and hsa_circ_0008410 were risk factors for RA. Therefore, PBMc hsa_circ_0000175, hsa_circ_0008410, and the combination of PBMc hsa_circ_0000175 and hsa_circ_0008410 may improve the diagnostic accuracy for RA. In addition, the expression levels of PBMc hsa_circ_0000175 and hsa_circ_0008410 were associated with disease activity and severity of RA.

Current Status of Functional Studies on Circular RNAs in Rheumatoid Arthritis and Their Potential Role as Diagnostic Biomarkers

“…53 It has been reported that the expression of circRNA_09505 was positively associated with ESR and CRP levels in serum from RA patients. 30 Additionally, circ_0001200 levels 13 and circ_0008410 52 were positively associated with silk time, while circ_0008360 level 13 was negatively associated with the silk time. The results of correlation analysis indicated that these circRNAs may play critical roles in the pathogenesis mechanism of RA and be used as a biomarker of disease severity.…”

“…Accordingly, Luo et al investigated the predictive power of two circRNAs (circ_0000175 and circ_0008410) in PBMCs as a holistic panel for RA diagnosis. 52 The results showed the combined area under the ROC curve was 0.971, with 93.10% sensitivity and 93.33% specificity. Similarly, combined AUC for both circ_104871 and circ_003524 was 0.855, slightly higher than that of circ_10487 (AUC = 0.833).…”

Insights Into the Involvement of Circular RNAs in Autoimmune Diseases

“…However, the etiology and precise pathogenesis of RA remain to be fully elucidated. Substantial research has discovered that circRNAs, such as hsa_circ_0035197, hsa_circ_0000175, hsa_circRNA_104194, hsa_circ_0001200, hsa_circ_0000396, and hsa_circ_0130438, are clearly dysregulated in RA (59)(60)(61)(62)(63). It is worth noting that hsa_circ_0002715 was correlated with the joint pain score, the joint swelling score, RF, and anti-imine protein antibodies (60).…”

Long Noncoding RNAs and Circular RNAs in Autoimmune Diseases

“…The levels of circ_0000175 and circ_0008410 correlated with anti-citrullinated protein antibodies and tender joint count, respectively, suggesting their expression may improve the diagnostic accuracy for RA. Thus, the expression levels of the circ_0000175 and circ_0008410 correlate with disease activity and severity [ 56 ]. These results corroborate the role that circRNAs may exhibit in the regulation of expression of target pathways that influence the occurrence and development of RA.…”