Retinoids induce antagonism between FOXO3A and FOXM1 transcription factors in human oral squamous cell carcinoma (OSCC) cells.
Kwame Osei-SarfoLorraine J GudasPublished in: PloS one (2019)
To gain a greater understanding of oral squamous cell carcinoma (OSCC) we investigated the actions of all-trans-retinoic acid (RA; a retinoid), bexarotene (a pan-RXR agonist), and forkhead box (FOX) transcription factors in human OSCC-derived cell lines. RA and bexarotene have been shown to limit several oncogenic pathways in many cell types. FOXO proteins typically are associated with tumor suppressive activities, whereas FOXM1 acts as an oncogene when overexpressed in several cancers. RA and/or bexarotene increased the transcript levels of FOXO1, FOXO3A, and TRAIL receptors; reduced the transcript levels of FOXM1, Aurora kinase B (AURKB), and vascular endothelial growth factor A (VEGFA); and decreased the proliferation of OSCC-derived cell lines. Also, RA and/or bexarotene influenced the recruitment of FOXO3A and FOXM1 to target genes. Additionally, FOXM1 depletion reduced cell proliferation, decreased transcript levels of downstream targets of FOXM1, and increased transcript levels of TRAIL receptors. Overexpression of FOXO3A decreased proliferation and increased binding of histone deacetylases (HDACs) 1 and 2 at the FOXM1, AURKB, and VEGFA promoters. This research suggests novel influences of the drugs RA and bexarotene on the expression of FOXM1 and FOXO3A in transcriptional regulatory pathways of human OSCC.
Keyphrases
- transcription factor
- endothelial cells
- dna binding
- rheumatoid arthritis
- vascular endothelial growth factor
- signaling pathway
- genome wide identification
- cell proliferation
- disease activity
- pi k akt
- rna seq
- pluripotent stem cells
- induced pluripotent stem cells
- ankylosing spondylitis
- induced apoptosis
- poor prognosis
- cell cycle arrest
- interstitial lung disease
- gene expression
- cell therapy
- systemic sclerosis
- stem cells
- bone marrow
- oxidative stress
- mass spectrometry
- systemic lupus erythematosus
- single molecule