Related Experiment Video
Updated: Nov 29, 2025
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
LncRNA GAS5 alleviates rheumatoid arthritis through regulating miR-222-3p/Sirt1 signalling axis
Zhou Yang1, Shu-Dian Lin1, Feng Zhan1
1Department of Rheumatology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, P. R. China.
Introduction:
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) GAS5 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 GAS5 in RA.
Methods:
The expression levels of GAS5, 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 GAS5 or Sirt1 and miR-222-3p was predicted by starBase and validated by dual-luciferase reporter assay.
Results:
GAS5 expression was found to be downregulated in the serum samples of RA patients and in RA-FLSs. GAS5 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, GAS5 indirectly regulates Sirt1 expression by binding miR-222-3p. Further experiments confirmed that Sirt1 overexpression restored the anti-RA activity of GAS5 under miR-222-3p mimic.
Conclusions:
The miR-222-3p/Sirt1 axis was found to be critical for the function of GAS5 in regulating the proliferation, inflammation, and apoptosis of RA-FLSs. These data indicate GAS5 activation as a potential therapeutic strategy for RA progression.
Insights
This study reveals that the long noncoding RNA GAS5 is downregulated in rheumatoid arthritis (RA). Upregulating GAS5 can inhibit RA fibroblast-like synoviocyte activity, offering a potential therapeutic strategy for RA.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Rheumatoid arthritis (RA) is a prevalent autoimmune disease.
- Fibroblast-like synoviocytes (FLSs) in rheumatoid pannus are key drivers of RA pathogenesis.
- The long noncoding RNA (lncRNA) GAS5 is downregulated in RA, but its precise role is unclear.
Purpose of the Study:
- To investigate the role and underlying mechanisms of lncRNA GAS5 in rheumatoid arthritis.
- To explore the potential of GAS5 as a therapeutic target for RA.
Main Methods:
- Quantitative PCR (qPCR) for gene expression analysis (GAS5, miR-222-3p, Sirt1).
- Cell proliferation assays (CCK-8, BrdU) and apoptosis assessments (flow cytometry, western blotting).
- ELISA for inflammatory cytokines (TNF-α, IL-1β, IL-6) and dual-luciferase reporter assays to validate molecular interactions.
Main Results:
- GAS5 expression is significantly downregulated in RA patient serum and RA-FLSs.
- Overexpression of GAS5 or inhibition of miR-222-3p suppressed RA-FLS proliferation and inflammation while promoting apoptosis.
- GAS5 regulates Sirt1 expression indirectly via miR-222-3p, and Sirt1 can rescue GAS5's anti-RA effects under miR-222-3p mimic conditions.
Conclusions:
- The miR-222-3p/Sirt1 axis is crucial for GAS5's regulatory function in RA-FLSs.
- GAS5 activation presents a promising therapeutic avenue for mitigating RA progression.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
02:39lncRNA - Long Non-coding RNAs
02:39lncRNA - Long Non-coding RNAs
01:16TGF - β Signaling Pathway
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...