Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus

J Autoimmun. 2016 Dec;75:96-104. doi: 10.1016/j.jaut.2016.07.012. Epub 2016 Jul 29.

Abstract

Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. However, our knowledge of Systemic Lupus Erythematosus (SLE)-related lncRNAs remains limited. In the present study we investigated the contribution of the lncRNA NEAT1 to the pathogenesis of SLE. Here, we found NEAT1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, NEAT1 expression was induced by LPS via p38 activation. Silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified the involvement of NEAT1 in TLR4-mediated inflammatory process was through affecting the activation of the late MAPK signaling pathway. Importantly, there was a positive correlation between NEAT1 and clinical disease activity in SLE patients. In conclusion, the increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest lncRNA contributes to the pathogenesis of lupus and provides potentially novel target for therapeutic intervention.

Keywords: Cytokines; Long noncoding RNA; NEAT1; Systemic lupus erythematosus; TLR4.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cluster Analysis
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Gene Ontology
  • Humans
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / immunology*
  • RNA, Long Noncoding / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding