Pharmacoepigenomics circuits induced by a novel retinoid-polyamine conjugate in human immortalized keratinocytes.
Katerina GrafanakiIlias SkeparniasChristos K KontosDimitrios AnastasakisAigli KorfiatiGeorge C KyriakopoulosKonstantinos TheofilatosSeferina MavroudiGeorge MagoulasDionissios PapaioannouAndreas ScorilasConstantinos StathopoulosDenis DrainasPublished in: The pharmacogenomics journal (2021)
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.
Keyphrases
- genome wide
- genome wide identification
- endothelial cells
- protein protein
- bioinformatics analysis
- cell proliferation
- cell cycle arrest
- skin cancer
- induced apoptosis
- induced pluripotent stem cells
- anti inflammatory
- genome wide analysis
- small molecule
- poor prognosis
- pluripotent stem cells
- oxidative stress
- cell death
- cancer therapy
- endoplasmic reticulum stress
- copy number
- gene expression
- papillary thyroid
- cell free
- neoadjuvant chemotherapy
- transcription factor
- lymph node
- signaling pathway
- young adults
- circulating tumor
- newly diagnosed
- high density
- locally advanced