Noncoding RNAs in rheumatoid arthritis: modulators of the NF-κB signaling pathway and therapeutic implications

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation and gradual tissue destruction. New research has shown how important noncoding RNAs (ncRNAs) are for changing immune and inflammatory pathways, such as the WNT signaling pathway, which is important for activating synovial fibroblasts and osteoblasts to work. This article examines the current understanding of several ncRNAs, such as miRNAs, lncRNAs, and circRNAs, that influence NF-κB signaling in the pathogenesis of RA. We investigate how these ncRNAs impact NF-κB signaling components, altering cell proliferation, differentiation, and death in joint tissues. The paper also looks at how ncRNAs can be used as potential early detection markers and therapeutic targets in RA because they can change important pathogenic pathways. This study highlights the therapeutic potential of targeting ncRNAs in RA therapy techniques, with the goal of reducing inflammation and stopping disease progression. This thorough analysis opens up new possibilities for understanding the molecular foundations of RA and designing novel ncRNA-based treatments.

Keywords: NF-κB signaling pathway; noncoding RNAs; rheumatoid arthritis; synovial fibroblasts; therapeutic targets.

Figure 1

Mechanisms leading to ACPA-positive RA progression. (A) Neo-epitopes form in mucosa through post-translational modifications. (B) APCs present these peptides, triggering autoantibody production. (C) Stromal cells, APCs, and macrophages produce inflammatory factors, driving synovial inflammation. (D) Cytokines and immune responses contribute to cartilage and bone destruction.

Figure 2

Inflammatory cells in ACPA-negative RA. Fibroblasts, macrophages, T cells, B cells, and plasma cells create a proinflammatory environment, with FLS being crucial. Activated cells release cytokines (IL-1, IL-6, IL-17, TNF-α) and MMPs, leading to cartilage and bone degradation.

Figure 3

The NF-κB signaling pathway. (A) The IKK complex activates the canonical pathway by phosphorylating and degrading IκB, which results in the activation of NF-κB. (B) Activation of a Not canonical Pathway: The NF-κB-inducing kinase (NIK) initiates the activation of IKKα, which in turn generates and transports p52 and phosphorylates p100.

Figure 4

The process of circular RNA formation. There are three methods that give rise to circular RNAs: lariat-driven, intron-pairing-driven, and RBP-mediated circularization. Endogenous inverted repeat-derived circular RNAs (EIciRNAs) are composed of conserved exons and introns. Splicing generates circular intronic RNAs (ciRNAs) that possess a 7-nucleotide GU-rich region adjacent to the 5′ splice site and an 11-nucleotide C-rich motif at the branch point.

Figure 5

RA-associated circRNAs influence the NF-κB signaling pathway.