DTX2 promotes glioma development via regulation of HLTF
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Published:2024-01-02
Issue:1
Volume:19
Page:
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ISSN:1745-6150
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Container-title:Biology Direct
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language:en
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Short-container-title:Biol Direct
Author:
Li Ren,Chen Yang,Yang Biao,Li Ziao,Li Peize,Chen Yu,Li Jiayu,He Jianhang,Wu Yongqiang,Sun Yanqi,Wang Xiaogang,Guo Xiaolong,Zhang Wenju,Zhao Yuanli,Guo Geng
Abstract
Abstract
Background
Human Deltex 2 (DTX2) is a ubiquitin E3 ligase that functions as an oncogene and has been shown to participate in many human cancers. However, the role of DTX2 in glioma progression has remained obscure. In this study, we explore the mechanism underlying the function of DTX2 in glioma progression.
Methods
The associations between DTX2 expression and clinical characteristics of glioma were determined by bioinformatic analysis of data from The Cancer Genome Atlas and Human Protein Atlas. The expression of DTX2 in glioma tissues was detected using immunohistochemistry and western blotting. Lentivirus-mediated gene knockdown and overexpression were used to determine the effects of DTX2 and helicase-like transcription element (HLTF) on glioma cell proliferation and migration with CCK-8, cell colony formation, transwell, and wound healing assays; flow cytometry in vitro; and animal models in vivo. The interaction of the DTX2 and HLTF proteins was verified by immunoprecipitation assay and confocal microscopy.
Results
DTX2 was highly expressed in glioma samples, and this was correlated with worse overall survival. Silencing of DTX2 suppressed glioma cell viability, colony formation, and migration and induced cell apoptosis. In vitro ubiquitination assays confirmed that DTX2 could downregulate HLTF protein levels by increasing ubiquitination of the HLTF protein. We also observed that HLTF inhibited proliferation and migration of glioma cells. Subcutaneous xenografts with DTX2-overexpressing U87 cells showed significantly increased tumor volumes and weights.
Conclusions
We have identified DTX2/HLTF as a new axis in the development of glioma that could serve as a prognostic or therapeutic marker.
Graphical abstract
Funder
The National Natural Science Foundation of China
the Basic Research Program of Shanxi Province
Key Medical Scientific Research Projects of Shanxi Province
Four “Batches” Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province
Publisher
Springer Science and Business Media LLC
Subject
Applied Mathematics,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics,Immunology
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