Pharmacoepigenomics circuits induced by a novel retinoid-polyamine conjugate in human immortalized keratinocytes

Pharmacogenomics J. 2021 Dec;21(6):638-648. doi: 10.1038/s41397-021-00241-9. Epub 2021 Jun 18.

Abstract

Retinoids are widely used in diseases spanning from dermatological lesions to cancer, but exhibit severe adverse effects. A novel all-trans-Retinoic Acid (atRA)-spermine conjugate (termed RASP) has shown previously optimal in vitro and in vivo anti-inflammatory and anticancer efficacy, with undetectable teratogenic and toxic side-effects. To get insights, we treated HaCaT cells which resemble human epidermis with IC50 concentration of RASP and analyzed their miRNA expression profile. Gene ontology analysis of their predicted targets indicated dynamic networks involved in cell proliferation, signal transduction and apoptosis. Furthermore, DNA microarrays analysis verified that RASP affects the expression of the same categories of genes. A protein-protein interaction map produced using the most significant common genes, revealed hub genes of nodal functions. We conclude that RASP is a synthetic retinoid derivative with improved properties, which possess the beneficial effects of retinoids without exhibiting side-effects and with potential beneficial effects against skin diseases including skin cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Dose-Response Relationship, Drug
  • Gene Regulatory Networks
  • HaCaT Cells
  • Humans
  • Inhibitory Concentration 50
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Interaction Maps
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Spermine / analogs & derivatives*
  • Spermine / pharmacology
  • Spermine / toxicity
  • Transcriptome*
  • Tretinoin / analogs & derivatives*
  • Tretinoin / pharmacology
  • Tretinoin / toxicity

Substances

  • MicroRNAs
  • N1,N12-bis(retinoyl)spermine
  • Spermine
  • Tretinoin