Introduction This study aims to investigate the role of phosphoribosyl pyrophosphate synthetases 2 (PRPS2) in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms. Methods The expression patterns of PRPS2 were analyzed in databases, and its expression levels were validated by RT-qPCR. Stable cell lines with PRPS2 knockdown and overexpression were established. In addition, MTT and colony formation assays were conducted to determine cell proliferation. Western blotting and RT-qPCR assays were conducted to evaluate changes in PI3K/AKT signaling and cell cycle proteins. Furthermore, a cell line-derived xenograft animal model was utilized to confirm the roles of PRPS2 in vivo . Results An elevation of PRPS2 was observed in NSCLC samples, and its overexpression promoted NSCLC cell proliferation, while PRPS2 knockdown inhibited cell proliferation. Additionally, PRPS2 overexpression promoted the PI3K/AKT signaling pathway in NSCLC cells. Moreover, PRPS2 regulated the expression of downstream genes in the PI3K/AKT pathway. Consistently, PRPS2 knockdown suppressed NSCLC tumor growth in vivo . In addition, PRPS2 was found downregulated by the natural compound pristimerin in NSCLC cells. Conclusion PRPS2 promotes tumor growth of NSCLC through the regulation of the activation of the PI3K/AKT signaling pathway. Targeting PRPS2 may be a promising strategy for the therapy of NSCLC in the future.
Xu et al. (2026) studied this question.