Data from PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis

作者：Zijian Zhou, Xianyong Yin, Hao Sun, Jun Lu, Yuming Li, Yang Fan, Peng Lv, Min Han, Jing Wu, Shengjie Li, Zihao Liu, Hongbo Zhao, Haohan Sun, Hao Fan, Shan Wang, Tao Xin · 年份：2025 · DOI：10.1158/0008-5472.c.7676157 · 被引用次数：3 · 研究领域：RNA Research and Splicing、RNA modifications and cancer、Cancer-related molecular mechanisms research

<div>AbstractLong-standing evidence implicates glioma stem cells (GSC) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we have demonstrated that global lactylation was significantly elevated in GSCs compared with differentiated glioma cells. Polypyrimidine tract–binding protein 1 (PTBP1), a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.Significance:Glycolysis-induced lactylation enhances the function of PTBP1 to promote glioma stem cell maintenance, indicating that PTBP1 lacty...