microRNA‑23 inhibits inflammation to alleviate rheumatoid arthritis via regulating CXCL12

Abstract

Rheumatoid arthritis (RA) is a common systemic, inflammatory and autoimmune disorder. MicroRNAs (miRs) are strongly associated with the initiation and progression of RA. However, the functions and mechanisms underlying miR-23 in RA are not completely understood. Therefore, the present study aimed to investigate the molecular mechanisms underlying miR-23 in RA. A bioinformatics tool (StarBase) and a wide range of experimental assays, including reverse transcription-quantitative PCR, western blotting, luciferase reporter assays and ELISAs, were performed to investigate the biological role of miR-23 in RA. The results indicated that miR-23 was downregulated and chemokine C-X-C motif ligand 12 (CXCL12) was upregulated in RA samples compared with healthy samples. Furthermore, miR-23 overexpression suppressed inflammation via reducing TNF-α, IL-1β and IL-8 expression levels compared with the NC mimic group. Regarding the underlying mechanism, compared with NC mimic, miR-23 mimic decreased CXCL12 mRNA expression by binding to its 3'-untranslated region. Additionally, CXCL12 overexpression reversed miR-23 mimic-mediated effects on inflammation. NF-κB signaling is associated with inflammation. Therefore, the present study indicated that CXCL12 promoted inflammation by activating NF-κB signaling. In conclusion, miR-23 inhibited inflammation to alleviate RA by regulating CXCL12 via the NF-κB signaling pathway, which may serve as a potential target for the diagnosis and treatment of RA.

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“…In general, the log-fold change (logFC) of CXCL12 in AADs was significantly higher than in NAADs ( p < 0.001, Figure 6A ). Accumulating evidence demonstrates that CXCL12 upregulation was implicated in AADs including IPF [ 51 ], rheumatoid arthritis (RA) [ 52 ], and amyotrophic lateral sclerosis (ALS) [ 53 ]. Consistent with our findings, upregulation of CXCL12 was suggested to promote migration and proliferation of human lung fibroblast in IPF as well as to enhance monocytes infiltration into the synovial tissue in RA [ 51 , 52 ].…”

“…Accumulating evidence demonstrates that CXCL12 upregulation was implicated in AADs including IPF [ 51 ], rheumatoid arthritis (RA) [ 52 ], and amyotrophic lateral sclerosis (ALS) [ 53 ]. Consistent with our findings, upregulation of CXCL12 was suggested to promote migration and proliferation of human lung fibroblast in IPF as well as to enhance monocytes infiltration into the synovial tissue in RA [ 51 , 52 ]. Treatment with an antagonist of CXCR4, the receptor for CXCL12, extended lifespan, improved motor function, and led to weight loss in ALS in vivo [ 54 ].…”

The Anti-Inflammatory Effect of Cabbage Leaves Explained by the Influence of bol-miRNA172a on FAN Expression

“…miR-147 was shown to be engaged in inflammatory response induction, while its loss diminished joint inflammation in rats with pristine induced arthritis and reduced TNF-α, IL-6, MMP3, and MMP13 expression in vitro ( Jiang et al, 2021 ). Another study showed that microRNA 23 is engaged in RA pathogenesis by influencing the NF-κB signaling pathway and decreasing TNF-α, IL-1β and IL-8 expression in RA patients ( Gao et al, 2021 ).…”

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

“…The levels of miR-548a-3p in serum exosomes and PBMCs of RA patients are significantly downregulated and negatively correlated with the levels of RF, ESR, and CRP, suggesting that the miR-548a-3p/TLR4/NF-κB axis could be used as a biomarker for RA diagnosis and targets for therapy ( 113 ). Serum exosome miR-1915-3p expression is significantly elevated in RA patients with clinical remission and negatively associated with CRP levels, which may be a potential biomarker of disease activity in Korean RA patients ( 114 ). Exosomes participate in cell-to-cell communication via the packaging and shuttling of diverse cargo molecules (including miRNAs) to recipient cells and have a crucial role in autoimmune-related disorders ( 115 , 116 ).…”