Hsa-circ-0001859 Regulates ATF2 Expression by Functioning as an MIR-204/211 Sponge in Human Rheumatoid Arthritis

Abstract

Background. circRNAs are part of the competitive endogenous RNA network, which putatively function as miRNA sponges and play a crucial role in the development of numerous diseases. However, studies of circRNAs in rheumatoid arthritis (RA) disease are limited. This work aims to identify the expression pattern of circRNAs in synovial tissues and their inflammatory regulation mechanism. Methods. We first compared the mRNA expression in rheumatoid arthritis patients with that in healthy volunteers by GEO database mining to identify gene loci specifically expressed in synovial tissues. Functional enrichment algorithms were then used to draw the interactome diagram of circRNAs-miRNAs-mRNAs. Finally, loss-of-function and rescue assays of the candidate circRNAs were performed in vitro. Results. A total of 29 differentially expressed circRNAs related to rheumatoid arthritis were discovered. Silencing of hsa-circ-0001859 suppressed ATF2 expression and decreased inflammatory activity in SW982 cells. Hsa-circ-0001859 could compete with ATF2 for miR-204/211. Discussion. These findings indicate that hsa-circ-0001859 participates deeply in the process of chronic inflammatory disease in synovial tissue.