Open AccessPHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
Author(s) -
Xie Manyi,
Ji Zhe,
Bao Yaxing,
Zhu Yufu,
Xu Yang,
Wang Lei,
Gao Shangfeng,
Liu Zhiyi,
Tian Zilu,
Meng Qingming,
Shi Hengliang,
Yu Rutong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13639
Subject(s) - stathmin , phosphoprotein , glioma , protein kinase b , cell growth , biology , gene silencing , cancer research , regulator , phosphorylation , microbiology and biotechnology , biochemistry , gene
Abstract PHAP 1 (Putative HLA ‐ DR ‐associated protein 1), also termed acidic leucine‐rich nuclear phosphoprotein 32A ( ANP 32A), Phosphoprotein 32 (pp32) or protein phosphatase 2A inhibitor (I1 PP 2A), 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 PHAP 1 protein was highly expressed in glioma patients, especially in those with high‐grade disease. Publicly available data also revealed high levels of PHAP 1 were associated with poor prognosis in glioma patients. The functional studies showed that knock‐down of PHAP 1 suppressed the proliferation of glioma cells, while overexpression of PHAP 1 facilitated it. The iTRAQ proteomic analysis suggested that stathmin might be a potential downstream target of PHAP 1. Consistently, PHAP 1 knock‐down significantly decreased the expression of stathmin, while overexpression of PHAP 1 increased it. Also, the upstream negative regulator, p27, expression levels increased upon PHAP 1 knock‐down and decreased when PHAP 1 was overexpressed. As a result, the phosphorylated Akt (S473), an upstream regulator of p27, expression levels decreased upon silencing of PHAP 1, but elevated after PHAP 1 overexpression. Importantly, we demonstrate the p27 down‐regulation, stathmin up‐regulation and cell proliferation acceleration induced by PHAP 1 overexpression were dependent on Akt activation. In conclusion, the above results suggest that PHAP 1 expression is elevated in glioma patients, which may accelerate the proliferation of glioma cells by regulating the Akt/p27/stathmin pathway.