LncRNA <i>GAS5</i> alleviates rheumatoid arthritis through regulating miR-222-3p/Sirt1 signalling axis

Rheumatoid arthritis (RA) is an autoimmune disease that affects millions of people. Fibroblast-like synoviocytes (FLSs) located in rheumatoid panni play a pivotal role in the formation of RA. The long noncoding RNA (lncRNA) <i>GAS5</i> is reportedly downregulated in rheumatoid arthritis. However, its detailed mechanism in RA remains to be explored. This study investigated the roles and related mechanisms of <i>GAS5</i> in RA. The expression levels of <i>GAS5</i>, miR-222-3p, and sirtuin 1 (Sirt1) were evaluated by quantitative PCR (qPCR). Cell proliferation was analyzed by CCK-8 and BrdU assays. Cell apoptosis was assessed by flow cytometry and western blotting. Enzyme-linked immunosorbent assay (ELISA) was utilized to evaluate the levels of TNF-α, IL-1β, and IL-6. The interaction between <i>GAS5</i> or Sirt1 and miR-222-3p was predicted by starBase and validated by dual-luciferase reporter assay. <i>GAS5</i> expression was found to be downregulated in the serum samples of RA patients and in RA-FLSs. <i>GAS5</i> overexpression or the inhibition of miR-222-3p impeded the activity of RA-FLSs by repressing their proliferation and inflammation and by promoting apoptosis. Mechanistically, <i>GAS5</i> indirectly regulates Sirt1 expression by binding miR-222-3p. Further experiments confirmed that Sirt1 overexpression restored the anti-RA activity of <i>GAS5</i> under miR-222-3p mimic. The miR-222-3p/Sirt1 axis was found to be critical for the function of <i>GAS5</i> in regulating the proliferation, inflammation, and apoptosis of RA-FLSs. These data indicate <i>GAS5</i> activation as a potential therapeutic strategy for RA progression.