Our study elucidates the link between nucleotide metabolism and RNA epigenetics in tumorigenesis through the PRPS2-MAT2A-WTAP/METTL3/METTL14 axis, providing potential insights for drug design and discovery in cancers associated with PRPS2 abnormalities, such as lung adenocarcinoma. The gene discussed is METTL3; the disease is cancer.