miR-449a inhibited TNFα-mediated YY1 and HMGB1 overexpression and IL-6 production and formed a mutual inhibition loop with YY1 in RA-FLS, which indicated that miR-449a was a crucial molecule in RA pathogenesis and acted as a switch to control TNFα-mediated inflammation. The gene discussed is HMGB1; the disease is rheumatoid arthritis.