Long non-coding RNA MIAT impairs neurological function in ischemic stroke via up-regulating microRNA-874-3p-targeted IL1B

Brain Res Bull. 2021 Oct:175:81-89. doi: 10.1016/j.brainresbull.2021.07.005. Epub 2021 Jul 13.

Abstract

Objective: Long non-coding RNAs (lncRNAs) have diagnostic and therapeutic values in the setting of ischemic stroke (IS). Here, we evaluated the value of myocardial infarction-associated transcript (MIAT) in IS with the involvement of microRNA (miR)-874-3p/interleukin (IL) 1B.

Methods: MIAT, miR-874-3p and IL1B levels in serum of patients with IS were measured. A middle cerebral artery occlusion (MCAO) model was established in mice. MCAO mice were injected with Agomir of miR-874-3p, shRNA or overexpression vector of MIAT or siRNA of IL1B. Subsequently, behavioral activities and neurological function of mice were assessed. The number of Nissl bodies, brain damage, neuronal apoptosis and inflammatory factors in brain tissues of mice were measured. The targeting relationship between MIAT and miR-874-3p, as well as that between miR-874-3p and IL1B was explored.

Results: In patients with IS, MIAT and IL1B were up-regulated and miR-874-3p was down-regulated. MIAT absorbed miR-874-3p while miR-874-3p targeted IL1B. Silencing of MIAT or IL1B, or promotion of miR-874-3p improved behavioral activities and neurological function of mice, reduced the number of Nissl bodies, as well as improved brain damage, neuronal apoptosis and inflammation. Overexpression of miR-874-3p abrogated up-regulated MIAT-mediated influence on MCAO mice.

Conclusion: Shortly, this study figures out that MIAT impairs neurological function in IS via up-regulating miR-874-3p-targeted IL1B.

Keywords: Behavioral activity; Interleukin 1B; Ischemic stroke; Long non-coding RNA myocardial infarction-associated transcript; Neurological function; microRNA-874-3p.

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / pathology
  • Female
  • Gene Silencing
  • Gene Targeting
  • Humans
  • Infarction, Middle Cerebral Artery / genetics
  • Infarction, Middle Cerebral Artery / pathology
  • Interleukin-1beta / blood
  • Interleukin-1beta / genetics*
  • Ischemic Stroke / genetics*
  • Ischemic Stroke / pathology
  • Ischemic Stroke / physiopathology*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Up-Regulation

Substances

  • IL1B protein, human
  • IL1B protein, mouse
  • Interleukin-1beta
  • MIRN874 microRNA, human
  • MIRN874 microRNA, mouse
  • Miat long non-coding RNA
  • MicroRNAs
  • RNA, Long Noncoding