LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a

Mol Cell Biochem. 2020 Mar;466(1-2):17-24. doi: 10.1007/s11010-019-03681-x. Epub 2020 Jan 1.

Abstract

Ankylosing spondylitis (AS) is a progressive systemic disease characterized by chronic inflammation response of the sacroiliac joint and spine. Long non-coding RNAs (lncRNAs) are widely involved in the regulation of various diseases. However, the role of lncRNA maternally expressed gene 3 (MEG3) in the inflammatory response of AS has not been studied. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues and cells. The expression levels of MEG3, microRNA-146a (miR-146a), and inflammatory cytokines were measured by quantitative real-time PCR (qRT-PCR). Correlation between MEG3 or miR-146a and inflammatory cytokines was analyzed by Pearson analysis. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to clarify the interaction between MEG3 and miR-146a. MEG3 was downregulated in AS patients, negatively correlated with the levels of IL-1β, IL-6, and TNF-α, and blocked the inflammatory response of AS. MiR-146a was upregulated in AS patients and could interact with MEG3. The expression of miR-146a was positively correlated with IL-1β, IL-6, and TNF-α levels. Overexpression of miR-146a reversed the inhibitory effect of abnormal MEG3 expression on inflammatory cytokines. LncRNA MEG3 plays an anti-inflammatory role in AS partially through targeting miR-146a, which provides a potential new means for the treatment of AS patients.

Keywords: Ankylosing spondylitis; Cytokines; Inflammatory response; MEG3; miR-146a.

MeSH terms

  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Gene Expression Regulation
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Spondylitis, Ankylosing / genetics
  • Spondylitis, Ankylosing / metabolism*
  • Spondylitis, Ankylosing / pathology
  • Spondylitis, Ankylosing / therapy

Substances

  • Cytokines
  • MEG3 non-coding RNA, human
  • MIRN146 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding