Study on the promoting effect of microplastic exposure on prostate cancer migration and invasion based on network toxicology and single-cell sequencing technology.

Authors

Haiyang Jiang, Ying Bi, Longguo Dai, Yong Zhu, Ruikang Zhang, Chen Hu, Hong Yang, Jun Li, Chongjian Zhang, Yu Bai, Ruiqian Li

Published in

Frontiers in oncology. Volume 16. Pages 1973812. Epub Oct 09, 2026.

Abstract

Prostate cancer (PCa) is a major malignant tumor threatening men's global health. The plasticizer acetyl tributyl citrate (ATBC), widely used as a substitute for phthalates, is increasingly detected in human tissues; however, its role in PCa cell migration and invasion and the underlying mechanisms remain largely unknown.
This study integrated network toxicology, scRNA-seq, transcriptomic analysis, Mendelian randomization (MR), and machine learning. In vitro, LNCaP cell proliferation, migration, and invasion were evaluated after ATBC treatment. ATBC toxicity targets were predicted using public databases. scRNA-seq data were analyzed to identify key cell clusters and candidate genes. Causal relationships between candidate genes and PCa were assessed by MR, and key genes were validated through multiple cohorts and HPA-based immunohistochemistry data. Molecular docking and virtual gene knockout were employed to explore binding affinity and functional impact.
In this study, in-vitro experiments were first performed, and it was found that the proliferation, migration and invasion abilities of ATBC-treated LNCaP cells were significantly altered. Subsequently, scRNA-seq data were analyzed to identify key cells (epithelial cells). Next, public databases were used to predict the toxic targets of ATBC, and the results of scRNA-seq and transcriptomic analyses were integrated to screen for potential target genes of ATBC in PCa. Finally, MR and machine-learning techniques were adopted to obtain the key genes (LPCAT1 and PDK1). In addition, molecular docking results for ATBC confirmed favorable binding affinity between the key genes and ATBC. Virtual knockout results also indicated that the key genes played a role in tumor migration and invasion.
ATBC exposure may promote PCa migration and invasion by targeting LPCAT1 and PDK1, thereby perturbing cytoskeletal dynamics and metabolic pathways. These findings offer novel mechanistic insights into microplastic-associated PCa progression.

PMID:
42920511
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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