LncRNA TUG1 reverses LPS-induced cell apoptosis and inflammation of macrophage via targeting MiR-221-3p/SPRED2 axis

Biosci Biotechnol Biochem. 2020 Dec;84(12):2458-2465. doi: 10.1080/09168451.2020.1806704. Epub 2020 Aug 25.


This study aimed to identify the role of lncRNA TUG1 with miR-221-3p on mice with lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Animal model was established, and lung tissue histopathologic status and permeability were detected by hematoxylin-eosin (HE) or Evans blue dye assay respectively. Levels of inflammation cytokines, lncRNA TUG1, miR-221-3p, sprouty related EVH1 domain-containing 2 (SPRED2), and phosphorylated (p)-ERK1/2 were determined by ELISA, qRT-PCR or Western blot. Pulmonary impairment and apoptosis were examined by flow cytometry. We observed that LPS up-regulated levels of tumor necrosis factor-α (TNF-α), Interleukin-1β (1L-1β), and ERK1/2 phosphorylation, and reduced SPRED2 levels, which were rescued by overexpressed lncRNA TUG1. StarBase and dual-luciferase reporter assay verified that miR-221-3p was targeted by lncRNA TUG1. MiR-221-3p could reverse the effect of lncRNA TUG1 on cell apoptosis, levels of TNF-α, IL-1β, SPRED2, and p-ERK1/2. Therefore, overexpressed lncRNA TUG1 attenuated LPS-induced pulmonary impairment in ARDS mice via regulating miR-221-3p/SPRED2 axis.

Keywords: LncRNA TUG1; acute respiratory distress syndrome; miR-221-3p; sprouty-related EVH1 domain-containing 2.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Cell Count
  • Female
  • Inflammation / genetics
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neutrophils / cytology
  • RAW 264.7 Cells
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / metabolism*


  • Lipopolysaccharides
  • MIRN221 microRNA, mouse
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • Spred2 protein, mouse
  • long non-coding RNA TUG1, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3