Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets

Cancer Lett. 2018 Aug 1;428:90-103. doi: 10.1016/j.canlet.2018.04.016. Epub 2018 Apr 20.

Abstract

MicroRNAs (miRNAs) are small, single-stranded, endogenous non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Due to their broad regulatory effects, the precisely regulated, spatial-specific and temporal-specific expression of miRNAs is fundamentally important to various biological processes including the immune homeostasis and normal function of both innate and adaptive immune response. Aberrance of miRNAs is implicated in the development of various human diseases, especially cancers. Increasing evidence has revealed a dysregulated expression pattern of miRNAs in autoimmune diseases, among which many play key roles in the pathogenesis. In this review we summarize these findings on miRNA dysregulation implicated in autoimmune diseases, focusing on four representative systemic autoimmune diseases, i.e. systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and dermatomyositis. The causes of the dysregulation of miRNA expression in autoimmune diseases may include genetic and epigenetic variants, and various environmental factors. Further understanding of miRNA dysregulation and its mechanisms during the development of different autoimmune diseases holds enormous potential to bring about novel therapeutic targets or strategies for these complex human disorders, as well as novel circulating or exosomal miRNA biomarkers.

Keywords: Dermatomyositis (DM); Epigenetic mechanisms; Immunity; Rheumatoid arthritis (RA); Systemic lupus erythematosus (SLE); Systemic sclerosis (SSc).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Circulating MicroRNA / antagonists & inhibitors
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics
  • Circulating MicroRNA / metabolism*
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / immunology
  • Exosomes / metabolism
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Liquid Biopsy / methods
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Circulating MicroRNA
  • Immunologic Factors