Potential Role of circRNA-HIPK3/microRNA-124a Crosstalk in the Pathogenesis of Rheumatoid Arthritis

Background: Circular RNA-HIPK3 (CircHIPK3) has been shown to be aberrantly expressed in a variety of diseases, contributing to disease initiation and progression. The aim of the present study is to investigate the role of the circHIPK3 RNA/microRNA-124a interaction in the pathogenesis of rheumatoid arthritis (RA).

Methods: This study included 79 RA patients and 30 control individuals. The patients involved were classified according to the disease activity score (DAS28) into mild (24 patients), moderate (24 patients), and severe (31 patients). Serum samples were collected to estimate the relative gene expression of circHIPK3 RNA and its target gene microRNA-124a by quantitative real time-PCR. Moreover, ELISA was used to detect the serum levels of monocyte chemoattractant protein-1 (MCP-1). Routine laboratory estimation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) was also done.

Results: In all grades of RA groups, there was a significantly substantial elevation of circHIPK3 RNA gene expression, with subsequent downregulation of miRNA-124a when compared to the control group. CircHIPK3 and microRNA-124a expression have been established to be inversely linked. Also, estimation of serum levels of MCP-1, ESR, CRP, and RF exhibited a significant increase in all grades of RA as compared to the control group.

Conclusion: CircHIPK3 and microRNA-124a might be regarded as key players in the pathogenesis of RA. The cross-talk between them appears to be responsible for inducing joint inflammation by increasing MCP-1 production. Targeting circHIPK3 and microRNA-124a, and their downstream adaptor molecules, poses a new challenge for RA therapy.