Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer

Abstract Acrylamide (ACR) is a common food and environmental contaminant with potential carcinogenicity, but its molecular role in the development of breast cancer (BC) remains unclear. This study employed a network toxicology and molecular docking strategy to explore the potential association betwe...

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Main Authors: Zhaoda Duan, Chunjiao Yu, Wenjie Yang, Wenhui Wang, Qi Zhang, Qiaoling Ruan, Rui Zhang, Yongfang Zhao, Shan Yan
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-06964-0
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author Zhaoda Duan
Chunjiao Yu
Wenjie Yang
Wenhui Wang
Qi Zhang
Qiaoling Ruan
Rui Zhang
Yongfang Zhao
Shan Yan
author_facet Zhaoda Duan
Chunjiao Yu
Wenjie Yang
Wenhui Wang
Qi Zhang
Qiaoling Ruan
Rui Zhang
Yongfang Zhao
Shan Yan
author_sort Zhaoda Duan
collection DOAJ
description Abstract Acrylamide (ACR) is a common food and environmental contaminant with potential carcinogenicity, but its molecular role in the development of breast cancer (BC) remains unclear. This study employed a network toxicology and molecular docking strategy to explore the potential association between ACR exposure and BC. Differentially expressed genes were first identified by comparing gene expression profiles between breast cancer and normal tissues. BC-related targets were then screened through integrated analysis of multiple databases and intersected with ACR-associated targets, resulting in 49 shared genes. Protein–protein interaction network construction and MCC algorithm analysis identified 10 core genes. GO and KEGG enrichment analyses revealed that these genes were mainly involved in pathways such as PI3K-Akt signaling, HIF-1 signaling, and ECM–receptor interactions. Molecular docking results suggested that ACR could bind to key targets including EGFR, FN1, JUN, and COL1A1. Molecular dynamics simulations demonstrated that the complexes remained structurally stable throughout the simulation. Pan-cancer and paired sample analyses further confirmed the aberrant expression of core genes in BC, and immunohistochemistry results supported their altered protein levels. These findings suggest that ACR may interfere with BC-related molecular mechanisms through multi-target and multi-pathway interactions, providing theoretical evidence for its potential carcinogenic role and future risk assessment.
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institution Kabale University
issn 2045-2322
language English
publishDate 2025-07-01
publisher Nature Portfolio
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series Scientific Reports
spelling doaj-art-ec7df2d1e3f64ad7973c77ade6ae51de2025-08-20T03:37:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-06964-0Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancerZhaoda Duan0Chunjiao Yu1Wenjie Yang2Wenhui Wang3Qi Zhang4Qiaoling Ruan5Rui Zhang6Yongfang Zhao7Shan Yan8Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityYunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical UniversityAbstract Acrylamide (ACR) is a common food and environmental contaminant with potential carcinogenicity, but its molecular role in the development of breast cancer (BC) remains unclear. This study employed a network toxicology and molecular docking strategy to explore the potential association between ACR exposure and BC. Differentially expressed genes were first identified by comparing gene expression profiles between breast cancer and normal tissues. BC-related targets were then screened through integrated analysis of multiple databases and intersected with ACR-associated targets, resulting in 49 shared genes. Protein–protein interaction network construction and MCC algorithm analysis identified 10 core genes. GO and KEGG enrichment analyses revealed that these genes were mainly involved in pathways such as PI3K-Akt signaling, HIF-1 signaling, and ECM–receptor interactions. Molecular docking results suggested that ACR could bind to key targets including EGFR, FN1, JUN, and COL1A1. Molecular dynamics simulations demonstrated that the complexes remained structurally stable throughout the simulation. Pan-cancer and paired sample analyses further confirmed the aberrant expression of core genes in BC, and immunohistochemistry results supported their altered protein levels. These findings suggest that ACR may interfere with BC-related molecular mechanisms through multi-target and multi-pathway interactions, providing theoretical evidence for its potential carcinogenic role and future risk assessment.https://doi.org/10.1038/s41598-025-06964-0Acrylamide exposureBreast cancerNetwork toxicologyMolecular docking
spellingShingle Zhaoda Duan
Chunjiao Yu
Wenjie Yang
Wenhui Wang
Qi Zhang
Qiaoling Ruan
Rui Zhang
Yongfang Zhao
Shan Yan
Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
Scientific Reports
Acrylamide exposure
Breast cancer
Network toxicology
Molecular docking
title Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
title_full Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
title_fullStr Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
title_full_unstemmed Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
title_short Network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
title_sort network toxicology and molecular docking reveal the potential link between acrylamide exposure and breast cancer
topic Acrylamide exposure
Breast cancer
Network toxicology
Molecular docking
url https://doi.org/10.1038/s41598-025-06964-0
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