Aberrant dysregulated circular RNAs in the peripheral blood mononuclear cells of patients with rheumatoid arthritis revealed by RNA sequencing: novel diagnostic markers for RA

Abstract

Circular RNAs (circRNAs) represent a newly identified class of non-coding RNAs that have been shown to be involved in several diseases, including autoimmune diseases. Two studies have revealed the aberrant circRNA expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA) by microarrays. However, due to the intrinsic defects of microarrays, such as their inability to detect unidentified circRNAs, we examined the circRNA expression profiles in the PBMCs from four RA patients and three healthy controls by RNA sequencing (RNA-seq) and further explored the value of circRNAs in diagnosing RA. The results showed 71 markedly dysregulated circRNAs, including 41 upregulated and 30 downregulated circRNAs; these data included several previously unidentified candidate circRNAs. Gene Ontology and pathway annotation revealed that the most altered pathways and genes were associated with inflammation and transcriptional activity, such as the TNF pathway. The selected dysregulated circRNAs were verified by qRT-PCR in the PBMCs of 32 RA patients and 20 healthy controls, and the results indicated that hsa_circ_0000396 and hsa_circ_0130438 were downregulated in the RA group versus the healthy group, consistent with the RNA-seq data. The area under the receiver operating characteristic curve indicated the diagnostic value of both circRNAs for RA. Our results identified aberrant dysregulated circRNAs in RA patients, including several identified circRNAs, and the diagnostic value of circRNAs for RA, suggesting the superiority of RNA-seq versus microarrays for screening differentially expressed circRNAs and further strengthening the potential diagnostic value of circRNAs for the diagnosis of RA.