MiR-539-5p inhibits the inflammatory injury in septic H9c2 cells by regulating IRAK3

Mol Biol Rep. 2022 Jan;49(1):121-130. doi: 10.1007/s11033-021-06849-1. Epub 2021 Nov 10.

Abstract

Background: MicroRNAs (miRNAs) have been confirmed to play a potential role in sepsis, but little is known about their role in sepsis-induced cardiomyopathy (SIC).

Methods: The model of septic cardiomyopathy was constructed with H9c2 cells induced by lipopolysaccharide (LPS), and the expression of miR-539-5p was detected by qRT-PCR assay. ELISA, CCK-8, EdU TUNEL analysis were performed to evaluate the role of miR-539-5p in inflammation response, viability, proliferation and apoptosis of LPS-treated H9c2 cells. Moreover, miRWalk and TargetScan prediction, and dual-luciferase reporter gene assays were carried out to predict and confirm the target of miR-539-5p. Furthermore, the effects of target on inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells mediated by miR-539-5p was further explored.

Results: The expression of miR-539-5p was obviously down-regulated in LPS-induced H9c2 cells. In addition, over-expression of miR-539-5p significantly inhibited the inflammation response, promoted viability and proliferation, and suppressed apoptosis of LPS-treated H9c2 cells. Moreover, interleukin-1 receptor-associated kinase 3 (IRAK3) was verified as a target of miR-539-5p by dual-luciferase reporter gene assay. Besides, IRAK3 was highly expressed in H9c2 cells transfected with miR-539-5p inhibitor detected with qRT-PCR and western blot assays. Furthermore, over-expression of IRAK3 partially weakened the effects of miR-539-5p mimic on the inflammation response, proliferation and apoptosis of LPS-induced H9c2 cells.

Conclusions: MiR-539-5p potentially plays an important role in the pathogenesis of LPS-induced sepsis by targeting IRAK3, suggesting that miR-539-5p may be a potential new target for the treatment of LPS-induced sepsis.

Keywords: Cardiac insufficiency; IRAK3; Inflammatory injury; MiRNA-539-5p; Sepsis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics*
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Lipopolysaccharides / adverse effects*
  • MicroRNAs / genetics*
  • Models, Biological
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Rats
  • Sepsis / genetics*
  • Sepsis / metabolism
  • Transfection

Substances

  • Lipopolysaccharides
  • MIRN539 microRNA, rat
  • MicroRNAs
  • Interleukin-1 Receptor-Associated Kinases