Dual targeting of CXCR4 and EZH2 in endometriosis
Summary: We recently showed that endometriotic peritoneal fluid (PF) altered the regulation of enhancer of zeste homolog 2 (EZH2) and H3K27me3. This study aimed to determine if PF by regulating EZH2/H3K27me3 modulated C-X-C chemokine receptor type 4 (CXCR4), a major chemokine involved in the prolife...
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| Language: | English |
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Elsevier
2025-04-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225004031 |
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| author | Sarah Brunty Kassey Wagner Taylor Fleshman Morgan Ruley Brenda Mitchell Nalini Santanam |
| author_facet | Sarah Brunty Kassey Wagner Taylor Fleshman Morgan Ruley Brenda Mitchell Nalini Santanam |
| author_sort | Sarah Brunty |
| collection | DOAJ |
| description | Summary: We recently showed that endometriotic peritoneal fluid (PF) altered the regulation of enhancer of zeste homolog 2 (EZH2) and H3K27me3. This study aimed to determine if PF by regulating EZH2/H3K27me3 modulated C-X-C chemokine receptor type 4 (CXCR4), a major chemokine involved in the proliferation and migration processes in endometriosis. Endometriotic PF induced the mRNA expression of CXCR4 and EZH2 and protein expression of H3K27me3 in human endometrial stromal cells (hESCs) and eutopic endometrium (Eu). CXCR4 inhibitor, AMD3100, decreased the PF-induced expression of these factors and reduced migration, but increased the proliferation of hESCs. In contrast, the EZH2 inhibitor, GSK126, decreased the expression of EZH2 and H3K27me3 and reduced proliferation, but increased the expression of CXCR4 and migration of hESCs. A combination of both inhibitors decreased the expression of CXCR4, EZH2, and H3K27me3, as well as reduced cell proliferation and migration. Our study suggests that targeting both CXCR4 (inflammation) and EZH2 (epigenetics) may be a better alternative for women with endometriosis. |
| format | Article |
| id | doaj-art-ffbe1aefd77d4069a8357ce0a876a41a |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-ffbe1aefd77d4069a8357ce0a876a41a2025-08-20T03:02:37ZengElsevieriScience2589-00422025-04-0128411214310.1016/j.isci.2025.112143Dual targeting of CXCR4 and EZH2 in endometriosisSarah Brunty0Kassey Wagner1Taylor Fleshman2Morgan Ruley3Brenda Mitchell4Nalini Santanam5Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV 25755, USA; Department of Biochemistry & Cellular and Molecular Biology, University of Tennessee, 1311 Cumberland Avenue, Knoxville, TN 37916, USADepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV 25755, USADepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV 25755, USADepartment of Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV 25755, USADepartment of Obstetrics and Gynecology, Joan C. Edwards School of Medicine, Marshall University, One John Marshall Dr, Huntington, WV 25755, USADepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Avenue, Huntington, WV 25755, USA; Corresponding authorSummary: We recently showed that endometriotic peritoneal fluid (PF) altered the regulation of enhancer of zeste homolog 2 (EZH2) and H3K27me3. This study aimed to determine if PF by regulating EZH2/H3K27me3 modulated C-X-C chemokine receptor type 4 (CXCR4), a major chemokine involved in the proliferation and migration processes in endometriosis. Endometriotic PF induced the mRNA expression of CXCR4 and EZH2 and protein expression of H3K27me3 in human endometrial stromal cells (hESCs) and eutopic endometrium (Eu). CXCR4 inhibitor, AMD3100, decreased the PF-induced expression of these factors and reduced migration, but increased the proliferation of hESCs. In contrast, the EZH2 inhibitor, GSK126, decreased the expression of EZH2 and H3K27me3 and reduced proliferation, but increased the expression of CXCR4 and migration of hESCs. A combination of both inhibitors decreased the expression of CXCR4, EZH2, and H3K27me3, as well as reduced cell proliferation and migration. Our study suggests that targeting both CXCR4 (inflammation) and EZH2 (epigenetics) may be a better alternative for women with endometriosis.http://www.sciencedirect.com/science/article/pii/S2589004225004031Body substance sampleDiseaseEpigeneticsSmall moleculeTreatment |
| spellingShingle | Sarah Brunty Kassey Wagner Taylor Fleshman Morgan Ruley Brenda Mitchell Nalini Santanam Dual targeting of CXCR4 and EZH2 in endometriosis iScience Body substance sample Disease Epigenetics Small molecule Treatment |
| title | Dual targeting of CXCR4 and EZH2 in endometriosis |
| title_full | Dual targeting of CXCR4 and EZH2 in endometriosis |
| title_fullStr | Dual targeting of CXCR4 and EZH2 in endometriosis |
| title_full_unstemmed | Dual targeting of CXCR4 and EZH2 in endometriosis |
| title_short | Dual targeting of CXCR4 and EZH2 in endometriosis |
| title_sort | dual targeting of cxcr4 and ezh2 in endometriosis |
| topic | Body substance sample Disease Epigenetics Small molecule Treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225004031 |
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