Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking
Abstract Background Despite epidemiological studies linking phthalates to ovarian cancer, their multi-target molecular mechanisms remain unresolved, hindering biomarker discovery and preventive strategies. This study integrates network toxicology, multi-omics analyses, and molecular docking to syste...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01710-6 |
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| author | Junchan Yang Min Luo Hongjun Wang Jinfa Huang |
| author_facet | Junchan Yang Min Luo Hongjun Wang Jinfa Huang |
| author_sort | Junchan Yang |
| collection | DOAJ |
| description | Abstract Background Despite epidemiological studies linking phthalates to ovarian cancer, their multi-target molecular mechanisms remain unresolved, hindering biomarker discovery and preventive strategies. This study integrates network toxicology, multi-omics analyses, and molecular docking to systematically delineate phthalate-driven oncogenic pathways, thereby bridging mechanistic gaps and informing targeted interventions. Results We identified 234 potential targets related to phthalate exposure and ovarian cancer. Enrichment analysis revealed that these genes are associated with HIF-1 signaling, and metabolic pathways that promote cancer progression. Seven core genes were identified, with six (GAPDH, CASP3, PPARG, ESR1, CYCS, SIRT1, and CCND1) exhibiting differential expression in the TCGA ovarian cancer cohort. Single-cell analysis confirmed their widespread expression across various cell types, underscoring their roles in tumor biology. Molecular docking revealed specific binding interactions between phthalates and six core proteins. Conclusions Integrated computational analyses indicate that phthalates (DEP, DMP, DOP) may drive ovarian carcinogenesis through metabolic reprogramming (HIF-1α/glycolysis), strong binding to SIRT1/PPARα regulators, and tumor microenvironment remodeling. These findings establish a framework for prioritizing environmental carcinogens and identifying exposure biomarkers, with implications for reevaluating phthalate safety and elucidating the SIRT1-HIF1-PPARα axis in cancer pathogenesis. |
| format | Article |
| id | doaj-art-fe5ae80b020a487eb20eb950662c99fb |
| institution | DOAJ |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-fe5ae80b020a487eb20eb950662c99fb2025-08-20T02:40:15ZengBMCJournal of Ovarian Research1757-22152025-06-0118111410.1186/s13048-025-01710-6Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular dockingJunchan Yang0Min Luo1Hongjun Wang2Jinfa Huang3Department of Gynecology, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan)Department of Gynecology, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan)Department of Gynecology, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan)Department of Gynecology, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan)Abstract Background Despite epidemiological studies linking phthalates to ovarian cancer, their multi-target molecular mechanisms remain unresolved, hindering biomarker discovery and preventive strategies. This study integrates network toxicology, multi-omics analyses, and molecular docking to systematically delineate phthalate-driven oncogenic pathways, thereby bridging mechanistic gaps and informing targeted interventions. Results We identified 234 potential targets related to phthalate exposure and ovarian cancer. Enrichment analysis revealed that these genes are associated with HIF-1 signaling, and metabolic pathways that promote cancer progression. Seven core genes were identified, with six (GAPDH, CASP3, PPARG, ESR1, CYCS, SIRT1, and CCND1) exhibiting differential expression in the TCGA ovarian cancer cohort. Single-cell analysis confirmed their widespread expression across various cell types, underscoring their roles in tumor biology. Molecular docking revealed specific binding interactions between phthalates and six core proteins. Conclusions Integrated computational analyses indicate that phthalates (DEP, DMP, DOP) may drive ovarian carcinogenesis through metabolic reprogramming (HIF-1α/glycolysis), strong binding to SIRT1/PPARα regulators, and tumor microenvironment remodeling. These findings establish a framework for prioritizing environmental carcinogens and identifying exposure biomarkers, with implications for reevaluating phthalate safety and elucidating the SIRT1-HIF1-PPARα axis in cancer pathogenesis.https://doi.org/10.1186/s13048-025-01710-6PhthalatesMolecular dockingScCancerExplorerOvarian cancerNetwork toxicology |
| spellingShingle | Junchan Yang Min Luo Hongjun Wang Jinfa Huang Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking Journal of Ovarian Research Phthalates Molecular docking ScCancerExplorer Ovarian cancer Network toxicology |
| title | Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking |
| title_full | Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking |
| title_fullStr | Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking |
| title_full_unstemmed | Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking |
| title_short | Phthalates unleashed: decoding ovarian carcinogenesis through multi-omics networks, single-cell insights, and molecular docking |
| title_sort | phthalates unleashed decoding ovarian carcinogenesis through multi omics networks single cell insights and molecular docking |
| topic | Phthalates Molecular docking ScCancerExplorer Ovarian cancer Network toxicology |
| url | https://doi.org/10.1186/s13048-025-01710-6 |
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