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Updated: Dec 27, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Long non-coding RNA growth arrest-specific transcript 5 regulates rheumatoid arthritis by targeting
Ming Li1, Nana Wang1, Zilong Shen1
1Department of Orthopaedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Objectives:
It has been proved that fibroblast-like synoviocytes (FSs) play a critical role in the course of rheumatoid arthritis (RA), is a systemic autoimmune disease affecting multiple joints. Until now, no effective treatment has been established. Long non-coding RNA Growth Arrest-Specific Transcript 5 (GAS5) has been identified as a tumour-suppressor lncRNA in various cancers. However, the expression, biological role and clinical significance of GAS5 in RA is completely unknown. In this study, we test the hypothesis that GAS5 might inhibit proliferation and inflammatory response of FSs in RA.
Methods:
The expression of GAS5 was examined in synovial tissues from RA patients and normal individuals.
Results:
The expression of GAS5 was significantly reduced in RA synovial tissues and RA FSs, whereas the expression of homeodomain-interacting protein kinase 2 (HIPK2) was increased, indicating that it plays a critical role in inflammation and autoimmune diseases. We found that overexpression of GAS5 decreased the level of HIPK2, TNF-α and IL-6.
Conclusions:
The methylation-specific PCR results suggested that the GAS5 gene promoter was significantly methylated in RA synovial tissues and RA FSs. More importantly, treatment with methylation inhibitor 5-aza-2-deoxycytidine (5-azadC) inhibited hypermethylation of GAS5 promoter and expression of HIPK2. These results indicated that GAS5 regulates RA via potentially targeting HIPK2. Therefore, this study may provide a potential therapeutic target for RA.
Insights
Long non-coding RNA GAS5 is reduced in rheumatoid arthritis (RA) and may target HIPK2 to inhibit inflammation. Methylation inhibition of GAS5 shows potential for RA therapy.
Area of Science:
- Molecular Biology
- Immunology
- Rheumatology
Background:
- Fibroblast-like synoviocytes (FSs) are crucial in rheumatoid arthritis (RA) pathogenesis.
- No effective treatments currently exist for RA.
- Long non-coding RNA Growth Arrest-Specific Transcript 5 (GAS5) is a known tumor suppressor, but its role in RA is unexplored.
Purpose of the Study:
- Investigate the expression and function of GAS5 in RA.
- Test the hypothesis that GAS5 inhibits FSs proliferation and inflammation in RA.
Main Methods:
- Examined GAS5 expression in synovial tissues and FSs from RA patients and normal individuals.
- Assessed the impact of GAS5 overexpression on HIPK2, TNF-α, and IL-6 levels.
- Analyzed GAS5 promoter methylation in RA tissues using methylation-specific PCR.
- Evaluated the effect of a methylation inhibitor (5-azadC) on GAS5 methylation and HIPK2 expression.
Main Results:
- GAS5 expression was significantly reduced in RA synovial tissues and FSs.
- HIPK2 expression was elevated in RA tissues, inversely correlating with GAS5 levels.
- Overexpression of GAS5 decreased HIPK2, TNF-α, and IL-6 levels.
- GAS5 promoter hypermethylation was observed in RA tissues and FSs.
Conclusions:
- GAS5 expression is downregulated in RA, potentially due to promoter hypermethylation.
- GAS5 may regulate RA by targeting HIPK2, thereby modulating inflammatory responses.
- Restoring GAS5 expression or inhibiting its methylation could offer a novel therapeutic strategy for RA.
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