Dysregulated circular RNAs in rheumatoid arthritis: Cellular roles and clinical prospects

Rheumatoid arthritis (RA) is still a healthcare challenge, although current therapeutic strategies have substantially improved its clinical outcomes. The development of novel biomarkers and treatments can increase the likelihood of identification and disease remission in RA patients, especially for patients with seronegative RA and difficult-to-treat RA (D2T RA). Circular RNAs (circRNAs), a novel non-coding RNA species, have been reported to play crucial roles in various biological process of RA. The mechanistic functions of the dysregulated circRNAs in RA are primarily associated with miRNA sponging and regulating transcription. CircRNAs acting as miRNA sponges are further summarized by cell types, including fibroblast-like synoviocytes (FLSs), lymphocytes, macrophages, chondrocytes, and mesenchymal stem cells (MSCs)−/plasma−secreted exosomes. Besides, a description of dysregulated circRNAs in blood, synovial tissue and cartilage tissue suggests their diagnostic potential for RA. In addition, some directions for future research are provided to open the possibility that dysregulated cell- and tissue- specific circRNAs constituting a fresh reservoir of therapeutic targets, and biomarkers for diagnosis, predicting response to therapy, drug selection or patient stratification for RA.