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

Abstract

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.

MicroRNA implications in the etiopathogenesis of ankylosing spondylitis

“…Jiang and Wang () reported several critical observations regarding the participation of histone deacetylase (HDAC) 3 in the molecular mechanisms of AS. First, augmented mRNA and protein levels of HDAC3 and reduced levels of miRNA‐130a were found in PBMCs from AS patients.…”

“…In contrast, downregulation of let-7i suppressed IFN-γ production by anti-CD3 + anti-CD28+ LPS-stimulated AS T cells. Nonetheless, the downstream molecular mechanism of upregulated let-7i expression stimulating a T helper type 1 (Th1) (IFN-γ) immune response needs more detailed researches Jiang and Wang (2016). reported several critical observations regarding the participation of histone deacetylase (HDAC) 3 in the molecular mechanisms of AS.…”

MicroRNA-130a regulates chondrocyte proliferation and alleviates osteoarthritis through PTEN/PI3K/Akt signaling pathway

“…More importantly, it can prevent disturbance of normal immune function (8). Jiang and Wang (10) indicated that histone deacetylase 3 was involved in ankylosing spondylitis via miR-130a and enhancement of tumor necrosis factor-1α (TNF-1α) expression. Li et al (11) showed that miR-130a played an important role in regulating the expression of TNF-α in osteoarthritis.…”

Genetic and epigenetic etiology of autoimmune diseases: lessons from twin studies

“…Generally, a few surveys have inspected AS etiopathogenesis under the light of epigenetic aberrations. These studies focused on DNA methylation [110,111], histone modifications [112], and microRNAs [113][114][115][116]. Nonetheless, no study has evaluated the role of epigenetic dysregulation in susceptibility to AS applying twin pairs.…”