circPTPN22 as a novel biomarker and ceRNA in peripheral blood mononuclear cells of rheumatoid arthritis

The role of circular RNAs (circRNAs) in rheumatoid arthritis (RA) remains to be elucidated. To determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) and to identify novel biomarkers for RA and explore their potential effects in RA, the present study conducted high-throughput RNA sequencing to analyze circRNA expression profiles in PBMCs from 4 RA patients and 3 healthy controls (HCs). Reverse transcription-quantitative PCR was used to verify the expression of circPTPN22 in 42 RA patients, 44 HCs and 45 systemic lupus erythematosus (SLE) patients. In addition, bioinformatics analysis and Pearson's correlation test were conducted to assess the correlation of the relationships between circPTPN22 and RA progression. A receiver operating characteristic curve was calculated to evaluate the diagnostic value. Multilevel integrated analysis identified 41 upregulated and 30 downregulated circRNAs in RA patients compared with HCs. circPTPN22 was confirmed to be a common differentially expressed gene in RA and SLE compared with HCs. Area under the curve analysis suggested the diagnostic value of circPTPN22 expression to distinguish RA patients from both HCs and SLE patients. In addition, circPTPN22 levels in RA PBMCs were correlated with RA-IgG, RA-IgM, RA-IgA, anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor and C reactive protein levels. A total of four putative microRNAs (miRNAs or miRs), namely, hsa-miR-3074-5p, hsa-miR-373-3p, hsa-miR-766-3p and hsa-miR-34c-5p, were screened to be sponged by circPTPN22 via bioinformatics analysis and then experimentally verified to be upregulated in RA PBMCs compared with controls. The data suggested that circPTPN22 might be a novel biomarker for the diagnosis of RA and participate in RA pathogenesis through a sponge mechanism.

Automated summary

High-throughput RNA sequencing revealed differential expression of circRNAs in RA patients compared to HCs, with circPTPN22 identified as a common differentially expressed gene in RA and SLE. The expression of circPTPN22 demonstrated high diagnostic value in distinguishing RA patients from HCs and SLE patients. Furthermore, circPTPN22 levels were positively correlated with various RA-related factors in PBMCs.