Deciphering the Effect of Methyl 4‑Hydroxybenzoate on Breast Cancer by Bioinformatics and Experiments

Area of Science:

• Environmental Health
• Molecular Oncology
• Toxicology

Background:

• Methyl 4-hydroxybenzoate (MEP) is a common environmental contaminant linked to increased breast cancer (BRCA) risk.
• The precise molecular mechanisms underlying MEP's role in BRCA development are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which MEP may contribute to BRCA development.
• To identify potential biomarkers and therapeutic targets associated with MEP exposure in BRCA.

Main Methods:

• Utilized public health databases for differential expression analysis and network toxicology modeling.
• Performed protein-protein interaction mapping, gene set enrichment analysis, and immune infiltration profiling.
• Conducted molecular docking, single-cell transcriptomic analysis, and in vitro assays to assess MEP's effects.

Main Results:

• Identified CCNE1, CDK1, E2F1, and EZH2 as core oncogenic drivers in MEP-associated BRCA.
• MEP exposure enhanced malignant behaviors in MCF-7 cells and upregulated these four key genes.
• Fibroblasts were identified as the critical cellular context for biomarker expression during carcinogenesis.
• CCNE1 showed the highest predicted binding affinity to MEP, suggesting a potential therapeutic target.

Conclusions:

• MEP may promote BRCA development by targeting CCNE1, CDK1, E2F1, and EZH2 within fibroblasts.
• The CCNE1/CDK1 axis represents a potential therapeutic target for MEP-induced breast cancer.
• This research provides mechanistic insights into the environmental origins of breast cancer.