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CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis
Hui Yang, … , Xiuming Liang, Kun Lv
Hui Yang, … , Xiuming Liang, Kun Lv
Published November 16, 2021
Citation Information: JCI Insight. 2021;6(24):e146362. https://doi.org/10.1172/jci.insight.146362.
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Research Article Oncology

CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis

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Abstract

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.

Authors

Hui Yang, Xiaocen Liu, Xiaolong Zhu, Xueqin Li, Lan Jiang, Min Zhong, Mengying Zhang, Tianbing Chen, Mingzhe Ma, Xiuming Liang, Kun Lv

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Figure 2

CPVL expression is upregulated in glioma and is associated with poor patient prognoses.

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CPVL expression is upregulated in glioma and is associated with poor pat...
(A) Relative CPVL mRNA expression in normal brain specimens and glioma specimens of different clinical grades acquired from TCGA (n = 10 for normal, n = 100 for grade I, n =102 for grade II, n = 102 for grade III, n = 102 for grade IV). (B and C) The expression level of CPVL in normal brain cell (HEB and HBEC-5i) and glioma cell lines (U251, LN382, SHG44, A172, U118, T98G, and U87MG). (D) Western blotting analysis of CPVL expression in matched primary glioma tissues (T) and adjacent noncancerous tissues (ANT). The clinical grades of patientswere characterized (patient 1, grade II; patient 2, grade III; patient 3, grade I; patient 4, grade III; patient 5, grade IV). (E and F) The expression level of CPVL in normal brain specimens and glioma specimens of different clinical grades(n = 20 for normal, n = 45 for grade I, n = 78 for grade II, n = 32 for grade III, n = 24 for grade IV). (G) IHC staining analysis of CPVL protein expression in matched primary glioma tissues (T) and adjacent noncancerous tissues (ANT). Scale bars: 100 μm (200× magnification). (H) IHC staining analysis of CPVL protein expression in normal brain tissues and glioma tissues of different clinical grades. Scale bars: 100 μm (200× magnification, left panels) and 50 μm (400× magnification, right panels). Representative IHC images and IHC score quantification for CPVL are shown. (I–K) Kaplan-Meier survival curves show overall survival (I), progression-free survival (J), disease-free survival (K) of high CPVL–expressing and low CPVL–expressing glioma patients from the TCGA database. The clinical grades of patients were characterized (patient 1, grade II; patient 2, grade III; patient 3, grade I; patient 4, grade III; patient 5, grade IV).All experiments were repeated 3 times. β-Actin was used as a loading control. Bar graph data are presented as mean ± SD. One-way ANOVA with Dunnett’s multiple comparisons test (A, B, E, and H), 2-tailed Student’s t test (G), and log-rank test (I–K) analyses were performed. *P < 0.05.

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