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PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway

PHAP1 (Putative HLA‐DR‐associated protein 1), also termed acidic leucine‐rich nuclear phosphoprotein 32A (ANP32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1PP2A), is a multifunctional protein aberrantly expressed in multiple types of human cancers. However, its expression patt...

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Autores principales: Xie, Manyi, Ji, Zhe, Bao, Yaxing, Zhu, Yufu, Xu, Yang, Wang, Lei, Gao, Shangfeng, Liu, Zhiyi, Tian, Zilu, Meng, Qingming, Shi, Hengliang, Yu, Rutong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033192/
https://www.ncbi.nlm.nih.gov/pubmed/29667783
http://dx.doi.org/10.1111/jcmm.13639
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author Xie, Manyi
Ji, Zhe
Bao, Yaxing
Zhu, Yufu
Xu, Yang
Wang, Lei
Gao, Shangfeng
Liu, Zhiyi
Tian, Zilu
Meng, Qingming
Shi, Hengliang
Yu, Rutong
author_facet Xie, Manyi
Ji, Zhe
Bao, Yaxing
Zhu, Yufu
Xu, Yang
Wang, Lei
Gao, Shangfeng
Liu, Zhiyi
Tian, Zilu
Meng, Qingming
Shi, Hengliang
Yu, Rutong
author_sort Xie, Manyi
collection PubMed
description PHAP1 (Putative HLA‐DR‐associated protein 1), also termed acidic leucine‐rich nuclear phosphoprotein 32A (ANP32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1PP2A), is a multifunctional protein aberrantly expressed in multiple types of human cancers. However, its expression pattern and clinical relevance in human glioma remain unknown. In this study, Western blotting and immunohistochemistry analysis demonstrated PHAP1 protein was highly expressed in glioma patients, especially in those with high‐grade disease. Publicly available data also revealed high levels of PHAP1 were associated with poor prognosis in glioma patients. The functional studies showed that knock‐down of PHAP1 suppressed the proliferation of glioma cells, while overexpression of PHAP1 facilitated it. The iTRAQ proteomic analysis suggested that stathmin might be a potential downstream target of PHAP1. Consistently, PHAP1 knock‐down significantly decreased the expression of stathmin, while overexpression of PHAP1 increased it. Also, the upstream negative regulator, p27, expression levels increased upon PHAP1 knock‐down and decreased when PHAP1 was overexpressed. As a result, the phosphorylated Akt (S473), an upstream regulator of p27, expression levels decreased upon silencing of PHAP1, but elevated after PHAP1 overexpression. Importantly, we demonstrate the p27 down‐regulation, stathmin up‐regulation and cell proliferation acceleration induced by PHAP1 overexpression were dependent on Akt activation. In conclusion, the above results suggest that PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway.
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spelling pubmed-60331922018-07-06 PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway Xie, Manyi Ji, Zhe Bao, Yaxing Zhu, Yufu Xu, Yang Wang, Lei Gao, Shangfeng Liu, Zhiyi Tian, Zilu Meng, Qingming Shi, Hengliang Yu, Rutong J Cell Mol Med Original Articles PHAP1 (Putative HLA‐DR‐associated protein 1), also termed acidic leucine‐rich nuclear phosphoprotein 32A (ANP32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1PP2A), is a multifunctional protein aberrantly expressed in multiple types of human cancers. However, its expression pattern and clinical relevance in human glioma remain unknown. In this study, Western blotting and immunohistochemistry analysis demonstrated PHAP1 protein was highly expressed in glioma patients, especially in those with high‐grade disease. Publicly available data also revealed high levels of PHAP1 were associated with poor prognosis in glioma patients. The functional studies showed that knock‐down of PHAP1 suppressed the proliferation of glioma cells, while overexpression of PHAP1 facilitated it. The iTRAQ proteomic analysis suggested that stathmin might be a potential downstream target of PHAP1. Consistently, PHAP1 knock‐down significantly decreased the expression of stathmin, while overexpression of PHAP1 increased it. Also, the upstream negative regulator, p27, expression levels increased upon PHAP1 knock‐down and decreased when PHAP1 was overexpressed. As a result, the phosphorylated Akt (S473), an upstream regulator of p27, expression levels decreased upon silencing of PHAP1, but elevated after PHAP1 overexpression. Importantly, we demonstrate the p27 down‐regulation, stathmin up‐regulation and cell proliferation acceleration induced by PHAP1 overexpression were dependent on Akt activation. In conclusion, the above results suggest that PHAP1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway. John Wiley and Sons Inc. 2018-04-18 2018-07 /pmc/articles/PMC6033192/ /pubmed/29667783 http://dx.doi.org/10.1111/jcmm.13639 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xie, Manyi
Ji, Zhe
Bao, Yaxing
Zhu, Yufu
Xu, Yang
Wang, Lei
Gao, Shangfeng
Liu, Zhiyi
Tian, Zilu
Meng, Qingming
Shi, Hengliang
Yu, Rutong
PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title_full PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title_fullStr PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title_full_unstemmed PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title_short PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
title_sort phap1 promotes glioma cell proliferation by regulating the akt/p27/stathmin pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033192/
https://www.ncbi.nlm.nih.gov/pubmed/29667783
http://dx.doi.org/10.1111/jcmm.13639
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