MiR-152-3p regulates cell proliferation, invasion and extracellular matrix expression through by targeting FOXF1 in keloid fibroblasts

Life Sci. 2019 Oct 1:234:116779. doi: 10.1016/j.lfs.2019.116779. Epub 2019 Aug 17.

Abstract

Emerging evidence has revealed that microRNAs (miRNAs) play critical roles in keloid pathogenesis. However, potential molecular mechanism of keloid formation remains unclear. In the present study, our findings showed that miR-152-3p mRNA expression level was notably up-regulated in keloid tissues and keloid fibroblasts compared with that of normal skin tissues and normal skin fibroblasts, respectively. Furthermore, miR-152-3p inhibition remarkably suppressed cell proliferation, which was increased by miR-152-3p overexpression. Cell invasion was also significantly decreased by miR-152-3p inhibition, whereas was increased by miR-152-3p overexpression. The mRNA and protein expression levels of extracellular matrix components including type I collagen, type III collagen and fibronectin were decreased by miR-152-3p inhibition, but were increased by miR-152-3p overexpression. In addition, results of dual-luciferase reporter assay indicated that FOXF1 is a direct target of miR-152-3p. FOXF1 overexpression significantly inhibits cell proliferation, invasion, and extracellular matrix in keloid fibroblasts, and the suppressive effects of miR-152-3p mimic on these functions were notably partly reversed by FOXF1 overexpression. Taken together, these findings indicated that miR-152-3p regulates cell proliferation, invasion and extracellular matrix expression through targeting FOXF1 in keloid fibroblasts, suggesting that miR-152-3p is a novel and promising molecular target for keloid treatment.

Keywords: Cell proliferation; Extracellular matrix; FOXF1; Invasion; Keloid fibroblasts; miR-152-3p.

MeSH terms

  • 3' Untranslated Regions
  • Adolescent
  • Adult
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Extracellular Matrix / genetics
  • Extracellular Matrix / pathology*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation
  • Humans
  • Keloid / genetics
  • Keloid / pathology*
  • MicroRNAs / genetics*
  • Up-Regulation
  • Young Adult

Substances

  • 3' Untranslated Regions
  • FOXF1 protein, human
  • Forkhead Transcription Factors
  • MIRN152 microRNA, human
  • MicroRNAs