Related Experiment Video
Updated: Aug 2, 2025
Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
SNORD17-mediated KAT6B mRNA 2'-O-methylation regulates vasculogenic mimicry in glioblastoma cells
Jingyi Cui1,2, Xiaobai Liu2,3, Weiwei Dong2,3
1Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China.
Abstract:
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.
Insights
Researchers identified a new mechanism involving SNORD17, KAT6B, and ZNF384 that drives vasculogenic mimicry (VM) in glioblastoma (GBM). Targeting this axis offers a potential new strategy for treating GBM by inhibiting tumor blood supply.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma (GBM) is an aggressive primary brain tumor.
- Vasculogenic mimicry (VM) is a critical process in GBM tumor progression, forming tumor cell networks that supply blood.
- Understanding VM mechanisms is crucial for developing novel GBM therapeutic strategies.
Purpose of the Study:
- To elucidate the roles of SNORD17, KAT6B, and ZNF384 in GBM vasculogenic mimicry.
- To investigate the molecular interactions and regulatory pathways involved in VM.
- To evaluate the therapeutic potential of targeting the SNORD17/KAT6B/ZNF384 axis in GBM.
Main Methods:
- Quantitative PCR and Western blot to assess gene and protein expression.
- RTL-P and Immunoprecipitation (IP) assays to study molecular interactions (methylation and acetylation).
- Chromatin immunoprecipitation (ChIP) and luciferase reporter assays to validate gene transcription.
- In vivo xenograft mouse models to evaluate therapeutic efficacy.
Main Results:
- SNORD17 and ZNF384 were found to be upregulated, promoting VM in GBM.
- KAT6B was downregulated, inhibiting VM in GBM.
- The SNORD17/KAT6B/ZNF384 axis was confirmed to regulate VM by affecting VEGFR2 and VE-cadherin expression.
- Combined knockdown of SNORD17 and ZNF384 with KAT6B overexpression significantly reduced tumor growth and VM formation in vivo.
Conclusions:
- The SNORD17/KAT6B/ZNF384 axis plays a pivotal role in regulating vasculogenic mimicry in glioblastoma.
- This axis represents a novel therapeutic target for comprehensive GBM treatment.
- Modulating this pathway holds promise for improving patient survival and treatment outcomes in GBM.
