Uridine metabolism promotes lung adenocarcinoma progression by activating FBL transcription via YBX1 - PubMed
3 hours ago
- #Oncogenic Mechanism
- #Lung Adenocarcinoma
- #Uridine Metabolism
- Uridine metabolism is a compensatory pathway for tumor cells under glucose deprivation, but its role in tumor progression is not fully understood.
- Elevated uridine metabolism correlates with poor clinical outcomes in various cancers, especially in lung adenocarcinoma (LUAD).
- Single-cell RNA sequencing shows uridine metabolism promotes ribosome biogenesis and identifies YBX1 as the key transcription factor.
- Mechanistically, uridine metabolism induces lactylation of YBX1 at the K137 site, stabilizing the YBX1 protein.
- YBX1 activates FBL transcription by binding to its promoter, which modulates ribosome biogenesis.
- Silencing YBX1 or FBL inhibits tumor cell proliferation, migration, stemness in vitro, and reduces tumor growth in vivo.
- FBL knockdown can rescue the oncogenic effects of YBX1 overexpression, establishing a uridine metabolism-YBX1-FBL axis.
- These findings suggest this axis as a potential therapeutic target and could aid in metabolic profiling for personalized LUAD treatment.