Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that leads to systemic inflammation of diarthrodial joint, synovial hyperplasia, cartilage damage, and ultimately joint destruction and deformity. As the dominant non-immune cells in the synovium, fibroblast-like synoviocytes (FLSs) significantly contribute to the deterioration of RA. Our study aimed to explore the regulatory role of long non-coding RNA FOXD2-AS1 in RA progression. Compared to patients with joint trauma, the expression of FOXD2-AS1 was elevated in serum and synovial tissue samples of RA patients. FOXD2-AS1 knockdown inhibited the proliferation and invasion of rheumatoid FLSs but restored their apoptotic ability. Furthermore, FOXD2-AS1 acted as a sponge for microRNA (miR)-331-3p. The expressions of FOXD2-AS1 and miR-331-3p in synovial tissues of RA patients were negatively correlated. Protein inhibitor of activated STAT 3 (PIAS3) was predicted as a downstream target of miR-331-3p. The expressions of FOXD2-AS1 and PIAS3 in synovial tissues of RA patients were positively correlated, whereas a negative correlation was observed between the levels of miR-331-3p and PIAS3. Moreover, increased proliferation and invasion of rheumatoid FLSs induced by FOXD2-AS1 overexpression was inhibited by the knockdown of PIAS3. In summary, this study demonstrated that FOXD2-AS1 promoted RA progression via regulating the miR-331-3p/PIAS3 pathway, suggesting that therapeutic strategies based on the FOXD2-AS1/miR-331-3p/PIAS3 axis may represent a promising treatment approach for RA patients.