Rheumatoid arthritis (RA) is a systematic autoimmune disease that cardinally affects the joints and other organs. Many people all over the world are suffering from the disease and no effective treatment has been established. Fibroblast-like synoviocytes (FLSs) play a critical role in the occurrence and development of RA. Long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to participate in various cancers as a tumour suppressor. However, its clinical significance and biological role in RA is completely unknown.
RT-qPCR or FISH were used to examine the expression of FER1L4 NLRC5, FER1L4 and inflammatory cytokine levels in synovial tissues (STs) from patients with RA or RA FLSs. Western blot was applied to examine the expression of NLRC5 and inflammatory cytokine levels in synovial tissues (STs) from patients with RA or RA FLSs. BrdU staining and MTT assay were used to examine the cell proliferation ability. The methylation-specific PCR was performed to analyse the methylation levels.
The level of FER1L4 significantly reduced in STs and FLSs, whereas the nucleotide oligomerisation domain-like receptors 5 (NLRC5) levels were increased. Overexpression of FER1L4 can decreased the level of NLRC5 and inflammatory cytokine level. The FER1L4 gene promoter was significantly methylated in RA STs and FLSs. More importantly, treatment with methylation inhibitor 5-aza-2-deoxycytidine (5-azadC) inhibited hypermethylation of FER1L4 promoter and the expression of NLRC5.
These results indicated that FER1L4 regulates RA via targeting NLRC5 potentially. Therefore, this study may provide a candidate therapeutic target for RA.