Polystyrene nanoparticles promote endometrial cancer progression via downregulation of UGT1A genes

The widespread environmental presence of polystyrene nanoparticles (PS-NPs) and their potential health risks have become a growing concern. Concurrently, mortality rates associated with endometrial cancer (EC) have significantly increased in recent years. However, the impact of PS-NPs on the progression of EC remains insufficiently understood. This study investigates the specific biological effects of PS-NPs on EC cell lines and in vivo models. Our findings demonstrate that PS-NPs localize within lysosomes in EC cells and significantly enhance their migratory capacity in vitro. Further in vivo experiments utilizing a Balb/C nude mouse model revealed that exposure to PS-NPs accelerates the growth of EC tumors. Transcriptomic analysis of tumor tissues from PS-NPs-exposed mice showed significant alterations in pathways such as steroid hormone biosynthesis pathways, alongside a widespread downregulation of UGT1A family gene expression. Mechanistically, the targeted knockdown of UGT1A1 and UGT1A10 in EC cells significantly accelerated malignant progression, whereas the overexpression of these genes partially mitigated the malignant phenotype induced by PS-NPs exposure. Collectively, our findings show that PS-NPs promote EC progression by downregulating UGT1A genes (especially UGT1A1 and UGT1A10) and disrupting the homeostasis of the steroid hormone pathway. This research not only introduces a novel perspective for interdisciplinary studies bridging environmental toxicology and gynecological oncology but also provides critical scientific insights into understanding the pathogenesis of EC, developing prevention and treatment strategies, and assessing the safety of NPs.