This study aimed to investigate the molecular mechanisms underlying BPA(Bisphenol A)-induced cervical cancer, to identify core targets and signaling pathways, and to provide a theoretical basis for disease prevention and therapeutic intervention. The chemical structure of BPA was obtained from PubChem(Public Chemical Database), and its toxicity profile was evaluated using ProTox-3.0. Potential BPA-associated targets were predicted using multiple databases and subsequently standardized. Differentially expressed genes (DEGs) in cervical cancer were identified from Gene Expression Omnibus datasets using the R programming language and integrated with Weighted Gene Co-expression Network Analysis (WGCNA) to determine key module genes. The cervical cancer-related target set was then established. Common targets between BPA and cervical cancer were identified using Venn diagram analysis, and a protein-protein interaction (PPI) network was constructed to screen for core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore biological functions and pathways. Target gene expression was validated across multiple datasets, and molecular docking analysis was conducted using Cavity-Based Dock 2 (CB-Dock2). BPA exhibits endocrine toxicity and matrix metalloproteinase-mediated tissue damage, with 3 core targets identified across databases. In cervical cancer, 803 up-regulated and 1092 down-regulated DEGs were screened (|log2FC| ≥1, adjusted P <.05). WGCNA identified the turquoise module (normal group R = 0.98, P = 5 × 10-12; cancer group r = -0.98, P = 5 × 10-12), overlapping with 1110 DEGs. Nineteen common targets of BPA and cervical cancer were enriched in gene expression negative regulation and cancer pathways (hypergeometric test, false discovery rate (FDR) <0.05). PPI analysis confirmed Estrogen Receptor 1 (ESR1) and (Poly ADP-ribose Polymerase 1 (PARP1) as core targets: ESR1 was down-regulated (GSE122697: log2FC = -2.8, P <.0001; The Cancer Genome Atlas (TCGA): log2FC = -2.6, P <.0001), PARP1 up-regulated (GSE122697: log2FC = 3.1, P <.0001; TCGA: log2FC = 2.9, P = .0012). Both showed progressive expression changes with lesion advancement (GSE63514: ESR1 log2FC = -4.2, PARP1 log2FC = 4.5, P <.0001). Molecular docking revealed stable binding of BPA to ESR1 (-8.3 kcal/mol) and PARP1 (-8.5 kcal/mol, root-mean-square deviation RMSD <2.0 A). BPA may promote cervical carcinogenesis by interacting with ESR1 and PARP1 to regulate key cancer-related pathways. These targets may serve as potential biomarkers and therapeutic intervention points. Further experimental validation is required to confirm these findings.
Li et al. (Fri,) studied this question.