Long non-coding RNA growth arrest-specific transcript 5 regulates rheumatoid arthritis by targeting homeodomain-interacting protein kinase 2

Objective 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 rom 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-alpha and IL-6. Conclusion 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.