Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis
Bisphenols are widely found in plastic products and may be hazardous to human health due to their estrogenic effects. Bisphenols may be involved in the carcinogenic process through endocrine-disrupting properties, especially in breast cancer. However, the specific targets and mechanisms of bisphenol...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325008206 |
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| author | Baowen Yuan Yu Li Jinyuan Chang Chang Guo Wei Huang Yan Wang |
| author_facet | Baowen Yuan Yu Li Jinyuan Chang Chang Guo Wei Huang Yan Wang |
| author_sort | Baowen Yuan |
| collection | DOAJ |
| description | Bisphenols are widely found in plastic products and may be hazardous to human health due to their estrogenic effects. Bisphenols may be involved in the carcinogenic process through endocrine-disrupting properties, especially in breast cancer. However, the specific targets and mechanisms of bisphenols remain unclear. By integrating network toxicology, transcriptomics, and molecular docking technology, this study aims to methodically identify the possible targets and mechanisms of five bisphenols in causing breast cancer. Targets linked to breast cancer were screened using the disease database, and bisphenols targets were screened using the compound and its prediction database. Ultimately, 424 targets associated with bisphenols and breast cancer were selected. With the STRING database, Cytoscape, and enrichment analysis, 12 core targets were identified, which are predominantly engaged in chemical carcinogenesis - receptor activation and estrogen signaling pathway. Furthermore, 26 common differentially expressed genes, including the core target PGR, were found by transcriptomic analysis in human breast cancer cells exposed to four bisphenols. Molecular docking showed that the PGR protein and five bisphenols had the lowest binding energy (-7.7 ∼ -7.0 kcal/mol) and the highest binding affinity. This study suggests that bisphenols may bind to PGR and induce its expression, thus contributing to breast carcinogenesis. This may happen via chemical cancer-receptor activation, estrogen signaling pathway, and endocrine resistance pathway. This study offers a theoretical basis for disease prevention and control besides providing a new perspective on the pathogenic mechanism of environmental pollutants. It also promotes the application of the integrated research strategy of network toxicology, bioinformatics, and molecular docking technology in environmental pollutants research. |
| format | Article |
| id | doaj-art-f8a3067bac5e4f5f8eeb75fc8d414c19 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-f8a3067bac5e4f5f8eeb75fc8d414c192025-08-20T02:07:38ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0130011848010.1016/j.ecoenv.2025.118480Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysisBaowen Yuan0Yu Li1Jinyuan Chang2Chang Guo3Wei Huang4Yan Wang5State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaTraditional Chinese Medicine department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Corresponding author.Bisphenols are widely found in plastic products and may be hazardous to human health due to their estrogenic effects. Bisphenols may be involved in the carcinogenic process through endocrine-disrupting properties, especially in breast cancer. However, the specific targets and mechanisms of bisphenols remain unclear. By integrating network toxicology, transcriptomics, and molecular docking technology, this study aims to methodically identify the possible targets and mechanisms of five bisphenols in causing breast cancer. Targets linked to breast cancer were screened using the disease database, and bisphenols targets were screened using the compound and its prediction database. Ultimately, 424 targets associated with bisphenols and breast cancer were selected. With the STRING database, Cytoscape, and enrichment analysis, 12 core targets were identified, which are predominantly engaged in chemical carcinogenesis - receptor activation and estrogen signaling pathway. Furthermore, 26 common differentially expressed genes, including the core target PGR, were found by transcriptomic analysis in human breast cancer cells exposed to four bisphenols. Molecular docking showed that the PGR protein and five bisphenols had the lowest binding energy (-7.7 ∼ -7.0 kcal/mol) and the highest binding affinity. This study suggests that bisphenols may bind to PGR and induce its expression, thus contributing to breast carcinogenesis. This may happen via chemical cancer-receptor activation, estrogen signaling pathway, and endocrine resistance pathway. This study offers a theoretical basis for disease prevention and control besides providing a new perspective on the pathogenic mechanism of environmental pollutants. It also promotes the application of the integrated research strategy of network toxicology, bioinformatics, and molecular docking technology in environmental pollutants research.http://www.sciencedirect.com/science/article/pii/S0147651325008206BisphenolsBreast cancerNetwork toxicologyPGR |
| spellingShingle | Baowen Yuan Yu Li Jinyuan Chang Chang Guo Wei Huang Yan Wang Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis Ecotoxicology and Environmental Safety Bisphenols Breast cancer Network toxicology PGR |
| title | Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis |
| title_full | Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis |
| title_fullStr | Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis |
| title_full_unstemmed | Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis |
| title_short | Molecular mechanism of bisphenols induction of breast cancer through PGR revealed by network toxicology and transcriptomics integration analysis |
| title_sort | molecular mechanism of bisphenols induction of breast cancer through pgr revealed by network toxicology and transcriptomics integration analysis |
| topic | Bisphenols Breast cancer Network toxicology PGR |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325008206 |
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