Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches
BackgroundPolychlorinated biphenyls (PCBs) are environmental pollutants associated with various health issues, including breast cancer. This study investigates potential molecular mechanisms by which PCBs may influence breast cancer progression using computational and preliminary experimental approa...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604993/full |
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| author | Xiaoyu Yang Wenlong Liang Zhenchu Feng Guangyan Li Xi Chen Jianguo Zhang |
| author_facet | Xiaoyu Yang Wenlong Liang Zhenchu Feng Guangyan Li Xi Chen Jianguo Zhang |
| author_sort | Xiaoyu Yang |
| collection | DOAJ |
| description | BackgroundPolychlorinated biphenyls (PCBs) are environmental pollutants associated with various health issues, including breast cancer. This study investigates potential molecular mechanisms by which PCBs may influence breast cancer progression using computational and preliminary experimental approaches.MethodsWe conducted a differential expression analysis using the TCGA-BRCA dataset. PCBs-related toxicological targets were collected from the Comparative Toxicogenomics Database (CTD). Enrichment and pathway analyses identified candidate biological processes and pathways. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Single-cell expression levels of key targets were analyzed (GSE114727 dataset). Molecular docking predicted binding affinities of PCBs congeners with key targets. Cell experiments assessed gene expression changes upon PCBs exposure.ResultsWe identified 52 upregulated and 24 downregulated PCBs-related toxicological targets in breast cancer. Enrichment analysis highlighted potential associations with pathways such as PI3K-Akt, MAPK, and HIF-1, including genes like BRCA1, FGFR1, IGF1, AKT1, and EGF. PPI network analysis identified key hub genes like EZH2, EGF, BRCA1, AKT1, IL6, and TNF. Single-cell analysis suggested variable expression of key targets across immune cell types. Molecular docking predicted strong binding affinities of PCB 105 with EZH2 and EGF in silico. Pathway analysis indicated gene expression alterations in the PI3K-AKT and MAPK signaling upon PCBs exposure, though causal relationships remain to be validated.ConclusionOur integrated analysis proposes that PCBs exposure may perturb key molecular pathways in breast cancer. Computational findings implicate targets like EZH2 and EGF, while preliminary cell experiments support further investigation. These results highlight a need for mechanistic studies to confirm PCB-induced effects and their therapeutic relevance, underscoring environmental pollutants as potential risk factors in cancer. |
| format | Article |
| id | doaj-art-9d74e91f9b8f42fb9c3c49669c25c275 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-9d74e91f9b8f42fb9c3c49669c25c2752025-08-20T02:31:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16049931604993Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approachesXiaoyu YangWenlong LiangZhenchu FengGuangyan LiXi ChenJianguo ZhangBackgroundPolychlorinated biphenyls (PCBs) are environmental pollutants associated with various health issues, including breast cancer. This study investigates potential molecular mechanisms by which PCBs may influence breast cancer progression using computational and preliminary experimental approaches.MethodsWe conducted a differential expression analysis using the TCGA-BRCA dataset. PCBs-related toxicological targets were collected from the Comparative Toxicogenomics Database (CTD). Enrichment and pathway analyses identified candidate biological processes and pathways. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Single-cell expression levels of key targets were analyzed (GSE114727 dataset). Molecular docking predicted binding affinities of PCBs congeners with key targets. Cell experiments assessed gene expression changes upon PCBs exposure.ResultsWe identified 52 upregulated and 24 downregulated PCBs-related toxicological targets in breast cancer. Enrichment analysis highlighted potential associations with pathways such as PI3K-Akt, MAPK, and HIF-1, including genes like BRCA1, FGFR1, IGF1, AKT1, and EGF. PPI network analysis identified key hub genes like EZH2, EGF, BRCA1, AKT1, IL6, and TNF. Single-cell analysis suggested variable expression of key targets across immune cell types. Molecular docking predicted strong binding affinities of PCB 105 with EZH2 and EGF in silico. Pathway analysis indicated gene expression alterations in the PI3K-AKT and MAPK signaling upon PCBs exposure, though causal relationships remain to be validated.ConclusionOur integrated analysis proposes that PCBs exposure may perturb key molecular pathways in breast cancer. Computational findings implicate targets like EZH2 and EGF, while preliminary cell experiments support further investigation. These results highlight a need for mechanistic studies to confirm PCB-induced effects and their therapeutic relevance, underscoring environmental pollutants as potential risk factors in cancer.https://www.frontiersin.org/articles/10.3389/fphar.2025.1604993/fullpolychlorinated biphenylsbreast cancerimmune cell infiltrationTCGAmolecular dockingnetwork toxicology |
| spellingShingle | Xiaoyu Yang Wenlong Liang Zhenchu Feng Guangyan Li Xi Chen Jianguo Zhang Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches Frontiers in Pharmacology polychlorinated biphenyls breast cancer immune cell infiltration TCGA molecular docking network toxicology |
| title | Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches |
| title_full | Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches |
| title_fullStr | Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches |
| title_full_unstemmed | Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches |
| title_short | Molecular mechanisms of polychlorinated biphenyls in breast cancer: insights from network toxicology and molecular docking approaches |
| title_sort | molecular mechanisms of polychlorinated biphenyls in breast cancer insights from network toxicology and molecular docking approaches |
| topic | polychlorinated biphenyls breast cancer immune cell infiltration TCGA molecular docking network toxicology |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1604993/full |
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