Lnc-IL7R promotes the growth of fibroblast-like synoviocytes through interaction with enhancer of zeste homolog 2 in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease that affects 1% of the world's population. Although the precise mechanism of RA has yet to be elucidated, accumulating evidence suggests that fibroblast-like synoviocytes (FLSs) serve critical roles in the initiation and progression of RA. However, the underlying molecular mechanisms of FLS proliferation have yet to be elucidated. Long noncoding-interleukin-7 receptor (lnc-IL7R) has been recently identified, which is activated by lipopolysaccharide (LPS) stimulation and diminishes the LPS-induced inflammatory response. In the present study, gain-and loss-of-function assays were performed in order to investigate the role of lnc-IL7R in FLS. It is demonstrated, to the best of the authors' knowledge for the first time, that lnc-IL7R promotes cell proliferation, cell cycle progression and inhibits apoptosis in FLS. Further investigation identified that lnc-IL7 interacts with enhancer of zeste homolog 2 (EZH2) and is required for polycomb repressive complex 2 (PRC2)-mediated suppression, including cyclin-dependent kinase inhibitor 1A and cyclin-dependent kinase inhibitor 2A. Lnc-IL7R may be a promising therapeutic target for the treatment of RA.