Choi Kyoung-Min, Berard Brennon A, Yoon Je-Hyun, Kim Dohoon
Department of Oncology Science, University of Oklahoma, Oklahoma City, OK, USA.
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Exp Mol Med. 2025 Aug 14. doi: 10.1038/s12276-025-01402-7.
Uridine is the ubiquitous nucleoside form of the RNA base uracil. It occupies a prominent 'hub' position in energy metabolism; for example, it is metabolically linked to de novo pyrimidine biosynthesis and glycolysis and biologically linked to diverse processes, such as RNA synthesis/degradation and glycosylation. It is a vital interorgan 'currency' nutrient readily imported by mammalian cells, and its supplementation can exert both cytoprotective and toxic effects, for which the underlying mechanisms are poorly understood. Importantly, it is a route by which the decay of RNA can be repurposed as an alternative fuel source under nutrient-limiting conditions to aid in tumor initiation, development and metastasis. Here we explain how the upstream inputs and downstream metabolic fates of uridine influence cancer traits and illustrate both established and hypothetical strategies targeting uridine metabolism for cancer therapy.
尿苷是RNA碱基尿嘧啶普遍存在的核苷形式。它在能量代谢中占据着重要的“枢纽”位置；例如，它在代谢上与从头嘧啶生物合成和糖酵解相关联，在生物学上与多种过程相关联，如RNA合成/降解和糖基化。它是一种重要的器官间“流通”营养素，很容易被哺乳动物细胞摄取，其补充剂既能发挥细胞保护作用，也能产生毒性作用，但其潜在机制尚不清楚。重要的是，在营养限制条件下，RNA的降解可通过这一途径被重新利用为替代燃料来源，以促进肿瘤的起始、发展和转移。在这里，我们解释了尿苷的上游输入和下游代谢命运如何影响癌症特征，并阐述了针对尿苷代谢进行癌症治疗的既定策略和假设策略。
