Wnt信号通路
胶质瘤
癌症研究
连环素
信号转导
表型
基因沉默
生物
跨膜蛋白
细胞生物学
化学
受体
基因
生物化学
作者
Hui Yang,Hui Zhou,Minjie Fu,Hao Xu,Haoyu Huang,Min Zhong,Mengying Zhang,Wei Hua,Kun Lv,Guoping Zhu
标识
DOI:10.1016/j.ijbiomac.2024.129332
摘要
Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of β-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/β-catenin signaling pathway. Stimulation with the Wnt/β-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/β-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.
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