Downregulation of miR‑483‑5p inhibits TGF‑β1‑induced EMT by targeting RhoGDI1 in pulmonary fibrosis

Mol Med Rep. 2021 Jul;24(1):538. doi: 10.3892/mmr.2021.12177. Epub 2021 Jun 3.

Abstract

Transforming growth factor‑β1 (TGF‑β1)‑induced epithelial‑mesenchymal transition (EMT) serves a significant role in pulmonary fibrosis (PF). Increasing evidence indicates that microRNAs (miRNAs or miRs) contribute to PF pathogenesis via EMT regulation. However, the role of miR‑483‑5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR‑483‑5p on TGF‑β1‑induced EMT in PF. It was found that the expression of miR‑483‑5p was upregulated in both PF tissue and A549 cells treated with TGF‑β1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR‑483‑5p mimic transfection promoted TGF‑β1‑induced EMT; by contrast, miR‑483‑5p inhibitor inhibited TGF‑β1‑induced EMT. Also, miR‑483‑5p mimic decreased RhoGDI1 expression, whereas miR‑483‑5p inhibitor increased RhoGDI1 expression. Furthermore, dual‑luciferase reporter gene assay indicated that miR‑483‑5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR‑483‑5p inhibitor on TGF‑β1‑induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway. In conclusion, these data indicated that miR‑483‑5p inhibition ameliorated TGF‑β1‑induced EMT by targeting RhoGDI1 via the Rac1/PI3K/Akt signaling pathway in PF, suggesting a potential role of miR‑483‑5p in the prevention and treatment of PF.

Keywords: TGF‑β1; epithelial‑​mesenchymal transition; microRNA‑483‑5p; pulmonary fibrosis.

MeSH terms

  • A549 Cells
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation / drug effects
  • rho Guanine Nucleotide Dissociation Inhibitor alpha / genetics*
  • rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism*

Substances

  • MIRN483 microRNA, human
  • MicroRNAs
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • rho Guanine Nucleotide Dissociation Inhibitor alpha

Grants and funding

The present study was supported by the National Major Science and Technology Projects of China (grant no. 2018ZX10302302003).