胶质瘤
癌症研究
基因沉默
细胞凋亡
STAT1
布鲁顿酪氨酸激酶
磷酸化
细胞生长
污渍
化学
信号转导
生物
细胞生物学
酪氨酸激酶
生物化学
基因
作者
Hui Yang,Xiaocen Liu,Xiaolong Zhu,Xueqin Li,Lan Jiang,Min Zhong,Mingjie Zhang,Tianbing Chen,M. Anthony Moody,Xiao Liang,Kun Lv
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2021-12-22
卷期号:6 (24)
被引量:12
标识
DOI:10.1172/jci.insight.146362
摘要
CPVL (carboxypeptidase, vitellogenic-like) is a serine carboxypeptidase that was first characterized in human macrophages. However, the function of CPVL remains unclear in a variety of tumors. The quantitative PCR (qPCR), Western blotting, and IHC assays were utilized to measure the CPVL expression. CPVL was significantly upregulated in glioma cells and tissues compared with normal cells and tissues, respectively. Moreover, high CPVL expression was correlated with advanced clinical grade and poor prognosis. Silencing of CPVL promoted glioma cell apoptosis, and it inhibited cell proliferation and tumorigenicity in vitro and in vivo. Ingenuity Pathway Analysis (IPA) demonstrated that CPVL silencing activated the IFN-γ/STAT1 signaling pathway, thereby inducing glioma cell apoptosis. Mechanistically, immunopurification, mass spectrometry, IP, and glutathione S-transferase (GST) pull-down experiments elucidated that CPVL physically interacts with Bruton's tyrosine kinase (BTK) and downregulates the STAT1 phosphorylation through promoting p300-mediated STAT1 acetylation. Our findings reveal the crucial role of CPVL in promoting the progression of glioma through suppressing STAT1 phosphorylation. CPVL might serve as a potential prognostic biomarker and therapeutic target for the treatment of glioma.
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