Rheumatoid arthritis (RA) is chronic inflammatory autoimmune disease. The crucial role of long non-coding RNA (lncRNA) in the progression of RA has been highlighted. Hence, this study was designed to explore the specific downstream mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in RA. Initially, the expression of NEAT1, p-p65, p300, and IL-18 in clinical tissues and cells was determined. Then, interactions among p65, NEAT1, p300, CBP, and IL-18 were investigated by immunofluorescence staining, dual luciferase reporter gene assay, RT-qPCR assay ChIP assay, and RIP assay followed by the analysis of their effects on RA in vivo and in vitro after expression alteration. The expressions of NEAT1, p-p65, p300, and IL-18 were all upregulated in the synovial tissues from the mice and patients with RA. NEAT1 silencing reduced the infiltration of CD4+ T cells and macrophages in synovial tissues, downregulated expression of blood inflammatory factors, relieved RA severity, and lowered incidence of RA in mice. Further, p-p65 could increase the expression of NEAT1 by binding to the NEAT1 promoter region, NEAT1 could co-locate and interact with p300, thus regulating the expression of IL-18 by regulating histone acetylation modification in IL-18 promoter region. NEAT1 aggravated RA via p300/CBP/IL-18 axis, representing a promising therapeutic target in RA.
Keywords: interleukin-18; long non-coding RNA nuclear-enriched abundant transcript 1; nuclear factor-kappa B; p300/CREB-binding protein; rheumatoid arthritis..
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