Role of histone deacetylase 3 in ankylosing spondylitis via negative feedback loop with microRNA-130a and enhancement of tumor necrosis factor-1α expression in peripheral blood mononuclear cells.

The present study was performed to investigate the molecular mechanism of ankylosing spondylitis (AS). The interaction between micro (mi)RNA‑130a and its target tumor necrosis factor (TNF)‑1α and histone deactylase (HDAC)3 was assessed in peripheral blood mononuclear cells (PBMCs) from AS patients. Increased HDAC3 and decreased miRNA‑130a levels were observed in PBMCs from AS patients. HDAC3 knockdown or HDAC3 inhibition promoted the expression of miRNA‑130a, and HDAC3 was recruited to the promoter region of the gene encoding miRNA‑130a in PBMCs. In addition, miR‑130a overexpression led to a decrease, whereas miR‑130a inhibition led to an increase of TNF‑1α expression in PBMCs. Furthermore, HDAC3 knockdown or HDAC3 inhibition was associated with simultaneous upregulation of the expression of miR‑130a and downregulation of the expression of TNF‑1α in PBMCs. These results indicated that HDAC3 was involved in the regulation of the underlying molecular mechanism of AS by forming a negative feedback loop with miR-130a and enhancement of TNF-1α expression.