Investigating the Role of the Posttranscriptional Gene Regulator MiR-24- 3p in the Proliferation, Migration and Apoptosis of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans

Cell Physiol Biochem. 2015;36(4):1359-70. doi: 10.1159/000430302.

Abstract

Aims: To explore the expression of miR-24-3p in human arteries with arteriosclerosis obliterans (ASO) as well as the role of miR-24-3p in the pathogenesis of ASO.

Methods: We used quantitative real-time PCR (qRT-PCR) and in situ hybridization to monitor miR-24-3p expression in human arteries. To investigate the effect of miR-24-3p on human arterial smooth muscle cells (HASMCs), we applied cell counting and EdU assays to monitor proliferation and transwell and wound healing assays to investigate migration and flow cytometry to investigate apoptosis. Furthermore, we applied 3'-untranslated region (3'-UTR) luciferase assays to investigate the role of miR-24-3p in targeting platelet-derived growth factor receptor B (PDGFRB) and c-Myc.

Results: MiR-24-3p was mainly located in the media of arteries and was downregulated in ASO arteries compared with normal arteries. Platelet-derived growth factor BB (PDGF-BB) treatment reduced the expression of miR-24-3p in primary cultured HASMCs. MiR-24-3p mimic oligos inhibited the proliferation and migration, and promotes apoptosis of HASMCs. Our 3'-UTR luciferase assays confirmed that PDGFRB and c-Myc were targets of miR-24-3p.

Conclusion: The results suggest that miR-24-3p regulates the proliferation and migration of HASMCs by targeting PDGFRB and c-Myc. The PDGF/miR-24-3p/PDGFRB and PDGF/miR-24-3p/c-Myc pathways may play critical roles in the pathogenesis of ASO. These findings highlight the potential for new therapeutic targets for ASO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Arteriosclerosis Obliterans / genetics*
  • Arteriosclerosis Obliterans / pathology
  • Base Sequence
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology*
  • Proto-Oncogene Proteins c-myc / genetics
  • Receptor, Platelet-Derived Growth Factor beta / genetics

Substances

  • MIRN24 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • Receptor, Platelet-Derived Growth Factor beta