Citation Information: JCI Insight. 2021. https://doi.org/10.1172/jci.insight.146362.
Abstract
CPVL (Carboxypeptidase, vitellogenic-like) is a serine carboxypeptidase which was first characterized in human macrophages. However, the function of CPVL remains unclear in a variety of tumors. The quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) assays were utilized to measure the CPVL expression. CPVL was significantly upregulated in glioma cells and tissues compared to 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, 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. Mechnistically, immunopurification, mass spectrometry, immunoprecipitation (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. For the first time, our findings revealed 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.
Authors
Hui Yang, Xiaocen Liu, Xiaolong Zhu, Xueqin Li, Lan Jiang, Min Zhong, Mengying Zhang, Tianbing Chen, Mingzhe Ma, Xiuming Liang, Kun Lv
