Polystyrene nanoparticles promote endometrial cancer development through the ACSS2-mediated reprogramming of arachidonic acid metabolism

Microplastics and nanoplastics are commonly found in our everyday environments. So far, microplastics and nanoplastics have been detected in various tissues and bodily fluids, including hair, sputum, digestive tissue, lungs, blood, placental and endometrial tissue. Although some studies indicate that microplastics and nanoplastics can promote tumor development, their impact on endometrial cancer (EC) remains unclear. In this study, we examined the effect of polystyrene nanoplastics (PS-NPs) on EC development and explored the underlying pathogenic mechanisms. We observed the uptake and accumulation of PS-NPs in HEC-1B cells and EC organoids. Through cell and organoid experiments as well as mouse models, we demonstrated that PS-NP exposure can accelerate EC progression in vitro and in vivo. Next, through transcriptomic sequencing and targeted metabolomic sequencing, We found that adenosine 5'-monophosphate-activated protein kinase (AMPK) can activate ACSS2 and promote its nuclear translocation. The nuclear entry of ACSS2 is associated with increased levels of H3K9 acetylation, which may be a potential mechanism through which it regulates PLA2G3 expression. PLA2G3 mRNA levels are upregulated, increasing the production of arachidonic acid (AA), and ultimately leads to the epithelial-mesenchymal transition (EMT) in EC cells. The relevant molecular markers in this study can provide new strategies for early warning and targeted intervention, reducing the potential impact of PS-NPs on EC.