MiR-326 regulates cell proliferation and apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis.

Abstract

The dysregulation of microRNAs plays a critical role in the development of rheumatoid arthritis (RA). This study aims to explore the functional significance of miR-326 in RA. TheRT-qPCR results showed that miR-326 was downregulated in synovial tissues of RA patients and RA fibroblast-like synoviocytes (RA-FLS). We found that miR-326 couldtarget and reduce the expression of inhibitor of DNA binding 1 (Id1). MTT assay and flow cytometry were conducted to explore the biological function of miR-326.Our datarevealed that the upregulation of miR-326suppressed cell proliferation and induced apoptosis in RA-FLS. Incollagen-induced arthritis mice,intraarticular injection of lentivirus carryingmiR-326overexpression vectors could reduce the arthritis score and attenuate synovial inflammation and cartilage destruction. We also found thatlong non-coding RNA-Ewing sarcoma-associated transcript 1 (lncRNA-EWSAT1) was significantly increased in RAsynovial tissues and RA-FLS. TheRNA immunoprecipitation and RNApull-down assay indicated thatlncRNA-EWSAT1 directly bound and negatively regulated the expression of miR-326.Knockdown of lncRNA-EWSAT1 could upregulatemiR-326 expression and attenuate its proliferation inhibition and apoptosis induction effect in RA-FLS. In conclusion,the lncRNA-EWSAT1/miR-326 axis might provide a novel therapeutic target in the treatment of RA.