Novel insights into the crosstalk between non-coding RNA and apoptosis in rheumatoid arthritis: diagnostic functions and therapeutic applications

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder and a leading cause of disability worldwide, significantly impairing patients' quality of life. As current therapeutic options remain limited, there is an urgent need for novel strategies, including the use of medicinal plants, to delay the development and progression of RA. Acute inflammation in RA is often accompanied by impaired apoptosis, which contributes to disease pathogenesis. With advances in high-throughput sequencing technologies, an increasing number of non-coding RNAs (ncRNAs) have been identified and extensively studied for their roles in both physiological and pathological processes. Dysregulation of these ncRNAs-particularly long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs)-has been implicated in various disorders, including RA. Given the well-established association between apoptosis and ncRNA expression in RA, a comprehensive understanding of their intricate interplay is essential. In this study, we systematically explore the complex interactions between lncRNAs and circRNAs in regulating apoptosis during the pathogenesis of RA. Additionally, we highlight emerging evidence, suggesting that ncRNA-mediated modulation of apoptosis can be achieved through herbal medicines, offering promising therapeutic avenues for RA treatment.

Keywords: TCM; apoptosis; ncRNAs; rheumatoid arthritis; therapeutic applications.

Figure 1

LncRNAs/circRNAs as RA diagnostic markers (by Figdraw). This figure summarizes the lncRNAs and circRNAs identified in distinct biological samples derived from RA patients, including serum, plasma, peripheral blood mononuclear cell (PBMCs), FLS, and synovial tissues.

Figure 2

The process of apoptosis (by Figdraw). This figure contrasts a normal cell (left panel) with the sequential stages of apoptosis and subsequent phagocytosis by macrophages (right panel), highlighting the absence of inflammatory responses during programmed cell death.

Figure 3

Major apoptosis signaling pathways participate in RA (by Figdraw). Schematic illustration of three pivotal signaling pathways involved in apoptosis regulation. The graphical representation delineates molecular cascades mediated by NF-κB signaling pathway, Wnt/β-catenin signaling pathway, and PI3K/Akt signaling pathway, highlighting their respective roles in cellular survival/death regulatory networks. Key molecular components are annotated to demonstrate pathway activation mechanisms and their functional convergence in apoptosis modulation.

Figure 4

LncRNAs play a ceRNA regulatory role in RA (by Figdraw). This figure delineates the intricate interplay between lncRNAs, miRNAs, and their downstream target genes or signaling pathways, with a focus on apoptosis regulation. These networks were curated from experimental and bioinformatic analyses, underscoring lncRNAs as central regulators of apoptosis-associated pathways. The diagram highlights potential therapeutic targets for RA, where dysregulated ncRNA interactions contribute to pathogenic mechanisms.

Figure 5

CircRNAs play a ceRNA regulatory role in RA (by Figdraw). This figure illustrates the ceRNA networks mediated by circRNAs, which sequester miRNAs to modulate the expression of downstream target genes involved in apoptosis. The diagram further integrates core apoptotic regulators, including Fas, Bax, caspase-3/9, and Bcl-2 family proteins, highlighting how circRNA-miRNA crosstalk fine-tunes cell fate decisions. These networks were constructed on the basis of RNA-seq, miRNA pull-down assays, and functional validations, underscoring circRNAs as critical nodes in apoptosis regulation. Dysregulation of these axes may contribute to diseases characterized by aberrant cell survival of RA.