PUM1 Promotes Tumor Progression by Activating DEPTOR‐Meditated Glycolysis in Gastric Cancer

• DOI: 10.1002/advs.202301190
• Publication Date: 2023-07-20T03:57:50Z
• Authors: Songcheng Yin; Huifang Liu; Zhijun Zhou; Xiaoyu Xu; Pengliang Wang; Wei Chen; Guofei Deng; Han Wang; Hong Yu; Liang Gu; Mingyu Huo; Min Li; Leli Zeng; Yulong He; Changhua Zhang
• Keywords: DEPTOR; gastric cancer; PUM1; Science; TOR Serine-Threonine Kinases; Q; Intracellular Signaling Peptides and Proteins; RNA-Binding Proteins; glycolysis; Mechanistic Target of Rapamycin Complex 1; 3. Good health; Phosphatidylinositol 3-Kinases; PI3K–Akt pathway; Stomach Neoplasms; Humans; Research Articles; Signal Transduction

RNA-binding proteins (RBPs) play essential roles in tumorigenesis and progression, but their functions gastric cancer (GC) remain largely elusive. Here, it is reported that Pumilio 1 (PUM1), an RBP, induces metabolic reprogramming through post-transcriptional regulation of DEP domain-containing mammalian target rapamycin (mTOR)-interacting protein (DEPTOR) GC. In clinical samples, elevated expression PUM1 associated with recurrence, metastasis, poor survival. vitro vivo experiments demonstrate knockdown inhibits the proliferation metastasis GC cells. addition, RNA-sequencing bioinformatics analyses show enriched glycolysis gene signature. Metabolomics studies confirm deficiency suppresses glycolytic metabolism. Mechanistically, binds directly to DEPTOR mRNA pumilio response element maintain stability transcript prevent degradation pathway. PUM1-mediated upregulation mTORC1 alleviates inhibitory feedback signal transmitted from PI3K under normal conditions, thus activating PI3K-Akt continuously. Collectively, these results reveal critical epigenetic role modulating DEPTOR-dependent progression. These conclusions support further investigation inhibitors as a metabolic-targeting treatment strategy for