PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway
| Autor: | Zhiyi Liu, Yaxing Bao, Zilu Tian, Yang Xu, Lei Wang, Rutong Yu, Zhe Ji, Shangfeng Gao, Yufu Zhu, Qingming Meng, Hengliang Shi, Manyi Xie |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics stathmin Blotting Western Stathmin 03 medical and health sciences 0302 clinical medicine Glioma Cell Line Tumor medicine Gene silencing Humans Protein kinase B Cell Proliferation biology Chemistry Cell growth Brain Neoplasms Akt Nuclear Proteins RNA-Binding Proteins p27 Cell Biology Protein phosphatase 2 Original Articles medicine.disease Prognosis Immunohistochemistry Gene Expression Regulation Neoplastic Stathmin Pathway 030104 developmental biology 030220 oncology & carcinogenesis Phosphoprotein PHAP1 Cancer research biology.protein Molecular Medicine Original Article Proto-Oncogene Proteins c-akt Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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