胶质母细胞瘤（GBM）具有高度侵袭性和致命性。 GBM 的失败凸显了开发更有效的靶向治疗策略的必要性。 KIF15是一种运动蛋白，参与细胞有丝分裂促进、细胞结构组装和细胞信号转导。 KIF15 在 GBM 中的精确生物学功能和潜在的上游调控机制仍然难以捉摸。在这里，我们证明 KIF15 在 GBM 中异常上调并预测 GBM 患者的不良预后。 KIF15 促进 GBM 细胞增殖、转移和细胞周期进展。 REST 可以结合 KIF15 启动子并反式激活 KIF15。此外，REST 与 P300 相互作用，并依赖其组蛋白乙酰转移酶 (HAT) 活性来共同调节 KIF15 表达。 REST和P300在GBM中均高表达，单独或与KIF15联合预测GBM患者预后不良。 KIF15在GBM中的致瘤功能在体外和体内均受到REST的调节，细胞周期抑制剂Palbociclib与P300 HAT抑制剂的联合治疗更显着地抑制GBM异种移植物的存活。我们的研究结果表明，KIF15 在 REST 和 P300 的协同反式激活下促进 GBM 进展。 P300/REST/KIF15 信号轴有望成为抗 GBM 候选治疗靶点的级联。© 作者。

Glioblastoma (GBM) is highly invasive and lethal. The failure to cure GBM highlights the necessity of developing more effective targeted therapeutic strategies. KIF15 is a motor protein to be involved in cell mitosis promotion, cell structure assembly and cell signal transduction. The precise biological function and the potential upstream regulatory mechanisms of KIF15 in GBM remain elusive. Here, we demonstrated that KIF15 was abnormally up-regulated in GBM and predicted poor prognosis of GBM patients. KIF15 promotes GBM cell proliferation, metastasis and cell cycle progression. REST could bind to KIF15 promoter and transactivate KIF15. Furthermore, REST interacts with P300 and depends on its histone acetyltransferase (HAT) activity to co-regulate KIF15 expression. Both REST and P300 were highly expressed in GBM and predicted poor prognosis of GBM patients alone or in combination with KIF15. The tumorigenic function of KIF15 in GBM was regulated by REST in vitro and in vivo and the combinational treatment of cell cycle inhibitor Palbociclib with P300 HAT inhibitor inhibited GBM xenografts survival more significantly. Our findings indicate that KIF15 promotes GBM progression under the synergistic transactivation of REST and P300. P300/REST/KIF15 signaling axis is expected to be served as a cascade of candidate therapeutic targets in anti-GBM.© The author(s).