Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and invasion via the TGF-β1/Smad3 signaling pathway

Biochem Biophys Res Commun. 2018 Jan 1;495(1):713-720. doi: 10.1016/j.bbrc.2017.10.070. Epub 2017 Oct 16.

Abstract

The molecular mechanism of the pathogenesis of keloids is still not known and the clinical management of keloids remains challenging. MiRNA (microRNA) is a novel class of small regulatory RNAs that has emerged as key post-transcriptional regulators of gene expression. MiRNAs participate in diverse biological processes of various skin diseases and function as key regulators in the occurrence and development of tumors. The purpose of this study was to investigate the involvement of miRNAs in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression between keloid and normal skin samples. We found that 46 miRNAs were upregulated and 28 miRNAs were downregulated in keloid compared with normal skin samples. We focused on miR-1224-5p, which has been reported to function in cancers, although the expression and mechanism of miR-1224-5p in keloids remain to be explored. Overexpression of miR-1224-5p led to inhibition of keloid fibroblast proliferation, promotion of apoptosis and decrease of migration and invasion. Our results suggest that downregulation of miR-1224-5p may be one of the mechanisms involved in the occurrence and development of keloids.

Keywords: Fibroblasts; Keloid; Skin tumor; TGF-β1/Smad3; miR-1224-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Cell Proliferation
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Keloid / pathology*
  • Keloid / physiopathology*
  • Male
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Signal Transduction
  • Skin / pathology
  • Skin / physiopathology
  • Smad3 Protein / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Cells, Cultured

Substances

  • MIRN1224 microRNA, human
  • MicroRNAs
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta1