Lycium barbarum polysaccharide suppresses uridine induced malignant progression of lung adenocarcinoma via UPP1 regulation

Lycium barbarum polysaccharide (LBP), derived from the fruit of Lycium chinense Mill., has been extensively studied for their potential health benefits in both dietary and medicinal contexts. Specifically, LBP exhibits various pharmacological properties, including anti-inflammatory, antioxidant, anti-aging, and anti-tumor effects. This study investigates the role of LBP in the inhibition of uridine metabolism induced epithelial-to-mesenchymal transition (EMT), which contributes to the proliferation and migration of lung adenocarcinoma (LUAD). A two-sample mendelian randomization study identified uridine having a causal relationship with lung cancer. UPP1 has a critical role in uridine metabolism, and we demonstrate knocking down UPP1 can significantly reducing LUAD cell proliferation, invasion, and migration, as well as reversing the EMT process. Notably, uridine supplementation restored the migration of UPP1 knockdown LUAD cells. Both in vitro and in vivo studies showed that LBP markedly impeded tumorigenesis and the EMT process in LUAD. Specifically, LBP administration reversed the uridine-induced EMT process by reducing UPP1 expression in LUAD cells. Transcriptome sequencing of LBP treated LUAD cell revealed substantial downregulation of UPP1, and correlated with suppressed cell migration. Collectively, uridine drives cell migration and EMT in lung adenocarcinoma, whereas LBP counters these effects by modulating UPP1. These findings provide new insights into targeting uridine metabolism for LUAD treatment. • Uridine is a novel causal factor for lung adenocarcinoma progression, promoting epithelial-mesenchymal transition (EMT). • Lycium barbarum polysaccharide (LBP) suppresses LUAD by downregulating UPP1, reversing uridine-induced EMT. • Transcriptomics identifies uridine metabolism and EMT as key pathways targeted by LBP in LUAD.