Glioblastoma（GBM）是颅内区的原发性肿瘤。血管生成性模仿（VM）是一种形成为肿瘤细胞提供血液支持的通道的过程，研究VM可以为GBM的临床靶向治疗提供新策略。在本研究中，我们发现SNORD17和ZNF384显著上调并促进GBM中的VM，而KAT6B下调并抑制GBM中的VM。我们进行了RTL-P测定以验证SNORD17对KAT6B的2'-O-甲基化；IP测定用于检测ZNF384的KAT6B醋酸化。此外，ZNF384与VEGFR2和VE-钙素连接蛋白的启动子区域的结合促进了转录，这经由染色质免疫沉淀和荧光素酶报告测定法得到验证。最后，SNORD17和ZNF384的沉默结合KAT6B的过表达有效地减小了异种移植瘤大小，延长了裸鼠的生存时间并减少了VM通道的数量。本研究揭示了SNORD17/KAT6B/ZNF384轴在修饰GBM中VM发展的新机制，这可能为GBM的全面治疗提供新目标。 © 2023。作者（们）独家许可Springer Nature B.V。

Glioblastoma (GBM) is a primary tumor in the intracranial compartment. Vasculogenic mimicry (VM) is a process in which a pipeline of tumor cells that provide blood support to carcinogenic cells is formed, and studying VM could provide a new strategy for clinical targeted treatment of GBM. In the present study, we found that SNORD17 and ZNF384 were significantly upregulated and promoted VM in GBM, whereas KAT6B was downregulated and inhibited VM in GBM. RTL-P assays were performed to verify the 2'-O-methylation of KAT6B by SNORD17; IP assays were used to detect the acetylation of ZNF384 by KAT6B. In addition, the binding of ZNF384 to the promoter regions of VEGFR2 and VE-cadherin promoted transcription, as validated by chromatin immunoprecipitation and luciferase reporter assays. And finally, knockdown of SNORD17 and ZNF384 combined with KAT6B overexpression effectively reduced the xenograft tumor size, prolonged the survival time of nude mice and reduced the number of VM channels. This study reveals a novel mechanism of the SNORD17/KAT6B/ZNF384 axis in modulating VM development in GBM that may provide a new goal for the comprehensive treatment of GBM.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.