Work

Atrazine-induced carcinogenesis in colorectal cancer: Core gene identification, immune cell infiltration, and cellular validation experiments

Year: 2025

Type: article

Abstract: OBJECTIVE: To explore the molecular mechanisms underlying the role of the environmental pollutant Atrazine in promoting colorectal cancer (CRC) tumorigenesis and progression. METHODS: The toxicological properties of Atrazine were evaluated using ADMETlab 3.0 and ProTox-3.0. Potential targets were predicted through SuperPred, TargetNet, SwissTargetPrediction, and STITCH databases, then intersected with CRC-related genes from GeneCards, TTD, and OMIM to identify candidate toxicological targets. GO, KEGG, and Metascape analyses were conducted to explore biological functions and signaling pathways. Transcriptomic data from the GEO database were integrated to construct 112 machine learning models for identifying Atrazine-related core genes. Gene expression and protein localization were verified through standardized mean difference analysis and the HPA database. A logistic regression-based nomogram was established to assess the diagnostic performance of core genes. Molecular docking using CB-Dock2 was applied to evaluate binding affinity between Atrazine and target proteins, while GSEA identified pathways associated with core gene expression. Immune infiltration and single-cell expression profiles were analyzed using CIBERSORT and TISCH2 databases. Finally, SHAP analysis was performed to determine the relative contribution of each gene to the predictive model, and in vitro assays were conducted to validate the functional effects of Atrazine exposure on CRC cells. RESULTS: Atrazine exhibited remarkable carcinogenicity and multi-system toxicity. Functional enrichment indicated significant involvement of candidate targets in oxidative stress, inflammation, apoptosis regulation, and immune evasion. Machine learning identified six core genes. Among them, MMP7, GSTP1, MIF, and ABCC1 were upregulated, while SGK1 and PTGS1 were downregulated in CRC. The nomogram model showed excellent predictive accuracy. SHAP analysis further revealed ABCC1, SGK1, and GSTP1 as key contributors, with ABCC1 exhibiting the highest SHAP value and the strongest binding affinity with Atrazine. CCK-8 and wound healing assays confirmed that Atrazine exposure enhanced CRC cell proliferation and migration, while qPCR analysis showed significant upregulation of ABCC1 expression in HCT116 and SW480 cells. CONCLUSION: Atrazine promotes CRC progression through multi-target and multi-pathway mechanisms. ABCC1 serves as the central gene linking Atrazine exposure to enhanced proliferation and migration of CRC cells.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119402

Authors: Laiming Mo, Siyang Yu, Huijun Zhu, Haiying Yue, Jiaying Wen

Institutions: The Seventh Affiliated Hospital of Sun Yat-sen University, Guangxi Medical University

Language: English

Topic: Carcinogens and Genotoxicity Assessment

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,650