Integrative analysis of DEHP exposure and prostate cancer: Mechanistic insights and predictive modeling.

OBJECTIVE

Di-(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer of significant health concern due to its endocrine disrupting effects. The study aims to elucidate underlying molecular mechanisms between DEHP exposure and prostate cancer (PCa).

METHODS

In vitro and in vivo experiments were undertaken to validate the effects of DEHP on the biological function of prostate cancer, and RNA sequencing was performed to elucidate the underlying mechanism. We integrated in silico toxicological assessments and bioinformatics methodologies was employed to investigate the key targets and associated downstream pathways in DEHP-induced PCa progression.

RESULTS

In vitro and in vivo experiments showed that MEHP promoted the proliferation, migration, and invasion of PCa cells and tumorigenicity, and RNA sequencing revealed that the metabolic pathways, pathways in cancer, PI3K-Akt signaling pathway, MAPK signaling pathway might be potential mechanisms involved in this process. Additionally, six DEHP-related genes were identified and a DEHP-related model was constructed. The data of scRNA indicated that these six DEHP-related genes may contribute in the tumor microenvironment of PCa. The molecular docking analysis revealed DEHP's ability to bind to crucial DEHP -related proteins.

CONCLUSIONS

Our study unveils a novel insight into the function for DEHP in PCa, shedding new light on prediction, assessment, and mitigation of DEHP exposure and PCa progression.