已经在多种肿瘤中评估了组蛋白赖氨酸特异性去甲基化酶1 (LSD1) 的表达情况，包括胃癌 (GC)。然而，LSD1 在 GC 中的调控机制尚不明确。本研究发现，神经前体细胞表达发育性下调蛋白8 (NEDD8) 被泛素连接酶 E2 M (UBE2M) 在 K63 上与 LSD1 共价结合，这种泛素化的 LSD1 可以促进 LSD1 的泛素化和降解，导致 GC 细胞干性和化疗抗性的降低。因此，我们的发现揭示了 LSD1 泛亚锁蛋白化的新机制及其对GC细胞干性和化疗抗性的贡献。综上所述，我们的发现可能对将来的泛亚锁蛋白化抑制剂的应用起到推动的作用。版权所有 © 2023。由 Elsevier B.V. 发布。

Histone lysine-specific demethylase 1 (LSD1) expression has been evaluated in multiple tumors, including gastric cancer (GC). However, the mechanisms underlying LSD1 dysregulation in GC remain largely unclear. In this study, neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) was identified to be conjugated to LSD1 at K63 by ubiquitin-conjugating enzyme E2 M (UBE2M), and this neddylated LSD1 could promote LSD1 ubiquitination and degradation, leading to a decrease of GC cell stemness and chemoresistance. Herein, our findings revealed a novel mechanism of LSD1 neddylation and its contribution to decreasing GC cell stemness and chemoresistance. Taken together, our findings may whistle about the future application of neddylation inhibitors.Copyright © 2023. Published by Elsevier B.V.