Cargando…
CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis
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....
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783677/ https://www.ncbi.nlm.nih.gov/pubmed/34784299 http://dx.doi.org/10.1172/jci.insight.146362 |
_version_ | 1784638583212081152 |
---|---|
author | Yang, Hui Liu, Xiaocen Zhu, Xiaolong Li, Xueqin Jiang, Lan Zhong, Min Zhang, Mengying Chen, Tianbing Ma, Mingzhe Liang, Xiuming Lv, Kun |
author_facet | Yang, Hui Liu, Xiaocen Zhu, Xiaolong Li, Xueqin Jiang, Lan Zhong, Min Zhang, Mengying Chen, Tianbing Ma, Mingzhe Liang, Xiuming Lv, Kun |
author_sort | Yang, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8783677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-87836772022-01-26 CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis Yang, Hui Liu, Xiaocen Zhu, Xiaolong Li, Xueqin Jiang, Lan Zhong, Min Zhang, Mengying Chen, Tianbing Ma, Mingzhe Liang, Xiuming Lv, Kun JCI Insight Research Article 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. American Society for Clinical Investigation 2021-12-22 /pmc/articles/PMC8783677/ /pubmed/34784299 http://dx.doi.org/10.1172/jci.insight.146362 Text en © 2021 Yang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Yang, Hui Liu, Xiaocen Zhu, Xiaolong Li, Xueqin Jiang, Lan Zhong, Min Zhang, Mengying Chen, Tianbing Ma, Mingzhe Liang, Xiuming Lv, Kun CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title | CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title_full | CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title_fullStr | CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title_full_unstemmed | CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title_short | CPVL promotes glioma progression via STAT1 pathway inhibition through interactions with the BTK/p300 axis |
title_sort | cpvl promotes glioma progression via stat1 pathway inhibition through interactions with the btk/p300 axis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783677/ https://www.ncbi.nlm.nih.gov/pubmed/34784299 http://dx.doi.org/10.1172/jci.insight.146362 |
work_keys_str_mv | AT yanghui cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT liuxiaocen cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT zhuxiaolong cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT lixueqin cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT jianglan cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT zhongmin cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT zhangmengying cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT chentianbing cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT mamingzhe cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT liangxiuming cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis AT lvkun cpvlpromotesgliomaprogressionviastat1pathwayinhibitionthroughinteractionswiththebtkp300axis |