胶质瘤
癌症研究
生物
EZH2型
连环素
病理
信号转导
医学
Wnt信号通路
表观遗传学
细胞生物学
生物化学
基因
作者
Zhiyuan Sun,Yufu Zhu,Feng Xia,Xiaoyun Liu,Kunlin Zhou,Qing Wang,Hengzhu Zhang,Hengliang Shi
出处
期刊:Cancers
[MDPI AG]
日期:2022-10-03
卷期号:14 (19): 4836-4836
被引量:2
标识
DOI:10.3390/cancers14194836
摘要
H3F3A K27M (H3.3K27M) is a newly identified molecular pathological marker in glioma and is strongly correlated with the malignancy of diffuse intrinsic pontine glioma (DIPG). In recent years, accumulating evidence has revealed that other types of glioma also contain the H3.3K27M mutation. However, the role of H3.3K27M in high-grade adult glioma, the most malignant glioma, has not been investigated. In this study, we focused on exploring the expression and function of H3.3K27M in high-grade glioma in adults. We found that H3.3K27M was highly expressed at high levels in some high-grade glioma tissues. Then, we introduced H3.3K27M into H3.3 wild-type glioma cells, U87 cells and LN229 cells. We found that H3.3K27M did not affect the growth of glioma cells in vitro and in vivo; however, the survival of mice with transplanted tumors was significantly reduced. Further investigation revealed that H3.3K27M expression mainly promoted the migration and invasion of glioma cells. Moreover, we confirmed that H3.3K27M overexpression increased the levels of the β-catenin and p-β-catenin (Ser675) proteins, the ubiquitin-specific protease 1 (USP1) mRNA and protein levels, and the enhancer of zeste homolog 2 (EZH2) protein level. In addition, the β-catenin inhibitor XAV-939 significantly attenuated the upregulation of the aforementioned proteins and inhibited the increased migration and invasion caused by the H3.3K27M mutation. Overall, the H3.3K27M mutation in high-grade glioma is a potential biomarker for poor prognosis mainly due to the infiltration of glioma cells that is at least partially mediated by the β-catenin/USP1/EZH2 pathway.
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