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pmid:37894370

Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma.

Małgorzata Chmielewska-Kassassir · Katarzyna Sobierajska · Wojciech M Ciszewski · Jakub Kryczka · Andrzej Zieleniak · Lucyna A Wozniak

Cancers · 2023 doi:10.3390/cancers15205003

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma.
doi
10.3390/cancers15205003
pmid
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Małgorzata Chmielewska-Kassassir
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Katarzyna Sobierajska
[2]
Wojciech M Ciszewski
[3]
Jakub Kryczka
[4]
Andrzej Zieleniak
[5]
Lucyna A Wozniak
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Cancers
year
2023
abstract
PURPOSE: To determine the mechanism of EPE in downregulating TYMS in MPM cancer. METHODS: The TYMS mRNA expression with epithelial-to-mesenchymal transition biomarkers and nuclear factor SP1 was assessed using the GEO database in a data set of MPM patients (GSE51024). Invasive MPM cell lines were in vitro models for the investigation of TYMS expression after EPE treatment. The tyms promoter SP1 binding sequences were determined using Genomatix v 3.4 software Electrophoretic mobility shift and dual-luciferase reporter assays revealed specific SP1 motifs in the interaction of EPE and reference compounds. Chromatin immunoprecipitation and Re-ChIP were used for the co-occupancy study. RESULTS: In MPM patients, a positive correlation of overexpressed TYMS with mesenchymal TWIST1, FN1 and N-cadherin was observed. EPE and its major components, gallic and ellagic acid (GA and EA, respectively), downregulated TYMS in invasive MPM cells by interacting with particular SP1 motifs on the tyms promoter. The luciferase constructs confirmed the occupation of two SP1 regulatory regions critical for the promotion of TYMS expression. Both EPE and reference standards influenced SP1 translocation into the nucleus. CONCLUSION: EPE components reduced TYMS expression by occupation of SP1 motifs on the tyms promoter and reversed the EMT phenotype of invasive MPM cells. Further in-depth analysis of the molecular docking of polyphenol compounds with SP1 regulatory motifs is required.
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