Profiling of differentially expressed circRNAs and functional prediction in peripheral blood mononuclear cells from patients with rheumatoid arthritis

Abstract

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with an increased risk of death, but its underlying mechanisms are not fully understood. Circular RNAs (circRNAs) have recently been implicated in various biological processes. The aim of this study was to investigate the key circRNAs related to RA. Methods A microarray assay was used to identify the differentially expressed circRNAs (DEcircRNAs) in peripheral blood mononuclear cells (PBMCs) from patients with RA compared to patients with osteoarthritis (OA) and healthy controls. Then, quantitative real-time PCR was applied to verify the DEcircRNAs, and correlations between the levels of DEcircRNAs and laboratory indices were analysed. We also performed extensive bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway and potential circRNA–miRNA–mRNA network analyses to predict the function of these DEcircRNAs. Results A total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR. There were correlations between the levels of DEcircRNAs and some of the laboratory indices. GO analyses revealed that these DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, cell cycle, posttranslational protein modification and collagen formation. Functional annotation of host genes of these DEcircRNAs was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, the AMPK signalling pathway, leukocyte transendothelial migration, platelet activation and the cAMP signalling pathway, which might be responsible for the pathophysiology of RA. Conclusions The findings of this study may help to elucidate the role of circRNAs in the specific mechanism underlying RA. Key messages Microarray assays showed that a total of 35,342 and 6146 DEcircRNAs were detected in RA patients compared to controls and OA patients, respectively. Nine out of the DEcircRNAs in RA were validated by real-time PCR, and the levels of the DEcircRNAs were related to some of the laboratory indices. GO analyses revealed that the DEcircRNAs in RA were closely related to cellular protein metabolic processes, gene expression, the immune system, etc. Functional annotation of host genes of the DEcircRNAs in RA was implicated in several significantly enriched pathways, including metabolic pathways, ECM–receptor interaction, the PI3K–Akt signalling pathway, etc.