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Toxicol Appl Pharmacol ; 451: 116180, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35907586

ABSTRACT

Protein tyrosine phosphatase non-receptor type 21 (PTPN21) has been recognised as a new tumour-associated protein that is implicated in diverse tumours. However, the correlation between PTPN21 and glioma remains unaddressed. This investigation focused on the relevance of PTPN21 in glioma. The Cancer Genome Atlas (TCGA) analysis identified PTPN21 as being up-regulated in glioma tissue. The elevation of PTP21 in glioma was validated by evaluating clinical specimen. Kaplan-Meier plot analysis revealed that a high PTPN21 level predicted poor survival rate in glioma patient. Silencing of PTPN21 produced remarkable anticancer effects in glioma cells including proliferation inhibition, cell cycle arrest, metastasis suppression and enhanced chemosensitivity. Mechanistic studies uncovered that PTPN21 contributes to mediation of the phosphatidyl-inositole-3 kinase (PI3K)/AKT pathway via the regulation of epidermal growth factor receptor (EGFR). Restraint of EGFR diminished PTPN21 overexpression-induced promoting effect on PI3K/AKT pathway. Reactivation of AKT reversed PTPN21 silencing-evoked antitumor effect. The tumorigenic potential of PTPN21-silenced glioma cells in vivo was markedly compromised. In summary, this study demonstrates that silencing of PTPN21 produces remarkable anticancer effects in glioma by restraining the EGFR/PI3K/AKT pathway.


Subject(s)
Glioma , Phosphatidylinositol 3-Kinases , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation , ErbB Receptors/genetics , ErbB Receptors/metabolism , Glioma/drug therapy , Glioma/genetics , Glioma/metabolism , Humans , Phosphatidylinositol 3-Kinases/metabolism , Phosphoric Monoester Hydrolases/metabolism , Protein Tyrosine Phosphatases, Non-Receptor/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
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