Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma
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...
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/20/5003 |
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| author | Małgorzata Chmielewska-Kassassir Katarzyna Sobierajska Wojciech M. Ciszewski Jakub Kryczka Andrzej Zieleniak Lucyna A. Wozniak |
| author_facet | Małgorzata Chmielewska-Kassassir Katarzyna Sobierajska Wojciech M. Ciszewski Jakub Kryczka Andrzej Zieleniak Lucyna A. Wozniak |
| author_sort | Małgorzata Chmielewska-Kassassir |
| collection | DOAJ |
| description | 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 <i>tyms</i> 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 <i>tyms</i> 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 <i>tyms</i> 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. |
| first_indexed | 2024-03-10T21:22:22Z |
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| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:22:22Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-38a0645dd22a4c41a1c9f4906fe9cf9c2023-11-19T15:59:11ZengMDPI AGCancers2072-66942023-10-011520500310.3390/cancers15205003Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural MesotheliomaMałgorzata Chmielewska-Kassassir0Katarzyna Sobierajska1Wojciech M. Ciszewski2Jakub Kryczka3Andrzej Zieleniak4Lucyna A. Wozniak5Department of Structural Biology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandDepartment of Molecular Cell Mechanisms, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, PolandInstitute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, PolandDepartment of Structural Biology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, PolandDepartment of Structural Biology, Medical University of Lodz, Żeligowskiego 7/9, 90-752 Lodz, PolandPurpose: 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 <i>tyms</i> 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 <i>tyms</i> 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 <i>tyms</i> 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.https://www.mdpi.com/2072-6694/15/20/5003malignant pleural mesotheliomaevening primrose extractthymidylate synthasespecificity protein 1 nuclear factorepithelial-to-mesenchymal transition |
| spellingShingle | Małgorzata Chmielewska-Kassassir Katarzyna Sobierajska Wojciech M. Ciszewski Jakub Kryczka Andrzej Zieleniak Lucyna A. Wozniak Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma Cancers malignant pleural mesothelioma evening primrose extract thymidylate synthase specificity protein 1 nuclear factor epithelial-to-mesenchymal transition |
| title | Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma |
| title_full | Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma |
| title_fullStr | Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma |
| title_full_unstemmed | Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma |
| title_short | Evening Primrose Extract Modulates TYMS Expression via SP1 Transcription Factor in Malignant Pleural Mesothelioma |
| title_sort | evening primrose extract modulates tyms expression via sp1 transcription factor in malignant pleural mesothelioma |
| topic | malignant pleural mesothelioma evening primrose extract thymidylate synthase specificity protein 1 nuclear factor epithelial-to-mesenchymal transition |
| url | https://www.mdpi.com/2072-6694/15/20/5003 |
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