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

Abstract

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. Conclusions: 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.

Role of m6A modification and novel circ_0066715/ miR-486-5p/ ETS1 axis in rheumatoid arthritis macrophage polarization progression

“…Notably, a co-expression relationship exists between circRNAs and miRNAs. After its transcription, circRNAs cooperate with miRNAs to participate in the regulation of RA [ 36 , 37 ]. There is also a regulatory relationship between circ_0066715 and miR-486 in this study.…”

Exploring regulatory mechanisms on miRNAs and their implications in inflammation-related diseases

“…Histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) also plays a role in RA pathogenesis by binding the promoter sites and bringing the H3K27me3 modification to the histone protein which suppresses miR-22-3p synthesis [ 50 ]. Circular RNA-HIPK3 (CircHIPK3) levels in RA patients correlate with the decrease in miR-124a [ 51 ]. In RA, many circular RNAs and miRNAs studied have the potential to be the biomarker of the disease state or the potential therapeutic target [ 72 ].…”

Fine‐tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis

“…Thus, it can control the differentiation of osteoclasts to affect ovariectomy‐induced bone resorption in mice. The experimental work of Saad el‐din (2022) and the group is the first one to evaluate the role of circHIPK3 RNA/miRNA‐124a in the pathogenesis of the autoimmune‐disorder RA. They concluded that overexpression of circHIPK3 in RA patients significantly enhances the disease severity by stimulating MCP‐1 (Monocyte Chemoattractant Protein‐1) secretion, mainly by acting as a sponge for miRNA‐124a, which is an antagonist of osteoclast differentiation (already discussed in the section 8.3.2.1).…”