MiR-5787 Attenuates Macrophages-Mediated Inflammation by Targeting TLR4/NF-κB in Ischemic Cerebral Infarction

Neuromolecular Med. 2021 Sep;23(3):363-370. doi: 10.1007/s12017-020-08628-w. Epub 2020 Nov 9.

Abstract

Accumulating studies have suggested the important role of microRNA (miRNA) in ischemic cerebral infarction. However, little is known of the modifying effect of miR-5787, a newly found miRNA, in ischemic cerebral infarction. We aim to elucidate the effect and underlying molecular mechanism of miR-5787 in the pathogenesis of ischemic cerebral infarction. MiR-5787 is demonstrated to be downregulated in peripheral blood mononuclear cells (PBMCs) samples of patients compared with controls, which is negatively associated with inflammatory cytokines of IL-6 and TNF-α in ischemic cerebral infarction. Besides, the expression of miR-5787 is also negatively related to TLR4, which is unregulated in PBMCs of ischemic cerebral infarction patients. Moreover, TLR4 is demonstrated to be a target of miR-5787 by bioinformatics' analysis and the luciferase reporter assay. In addition, miR-5787 can prevent from the proliferation and migration of macrophages, and attenuate LPS/TLR4-mediated inflammatory response via NF-κB in macrophages. MiR-5787 may be a promising biomarker for ischemic cerebral infarction.

Keywords: Inflammation; Ischemic cerebral infarction; Macrophages; MicroRNAs; NF-κb; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Division
  • Cell Movement
  • Cerebral Infarction / genetics*
  • Cerebral Infarction / metabolism
  • Female
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Macrophages / physiology*
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • Neuroinflammatory Diseases / genetics*
  • RNA, Messenger / biosynthesis
  • THP-1 Cells
  • Toll-Like Receptor 4 / antagonists & inhibitors*
  • Toll-Like Receptor 4 / genetics

Substances

  • IL6 protein, human
  • Interleukin-6
  • MIRN5787 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Messenger
  • TLR4 protein, human
  • Toll-Like Receptor 4