LncRNA MEG3 as a biomarker and therapeutic target in rheumatoid arthritis: Insights from gene polymorphisms, expression patterns, and functional mechanisms

Maternally expressed gene 3 (MEG3) is implicated in autoimmunity, but its role in rheumatoid arthritis (RA) is unclear. This study aimed to investigate gene polymorphisms, expression patterns, and functional mechanisms of MEG3 in RA pathogenesis and its clinical associations. MEG3 single nucleotide polymorphisms (SNPs) were genotyped in 551 RA patients and 595 controls, finding no association with RA susceptibility. MEG3 expression was downregulated in peripheral blood mononuclear cells (PBMCs) from RA patients, particularly in ACPA-positive cases, but increased with NSAID use. In fibroblast-like synoviocytes (FLS), MEG3 was downregulated. Overexpression of MEG3 inhibited FLS proliferation and invasion, lowering IL-1β and IL-6 but not TNF-α. Whereas MEG3 knockdown enhanced FLS proliferation and invasion, elevating TNF-α and IL-1β without altering IL-6. Collectively, MEG3 polymorphisms are not associated with RA susceptibility. MEG3 dysregulation correlates with RA clinical indicators and regulates FLS pathogenicity, indicating its potential as a clinical biomarker and therapeutic target in RA.