Protein phosphatase 1γ regulates the proliferation of human glioma via the NF-κB pathway
Zhen Bao1, Chengwei Duan2, Cheng Gong3
1Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China.
Abstract:
Protein phosphatase 1γ (PP1γ), a member of mammalian protein phosphatases, serine/threonine phosphatases, catalyzes the majority of protein dephosphorylation events and regulates diverse cellular processes, such as neuronal signaling, muscle contraction, glycogen synthesis, and cell proliferation. However, its expression and potential functions in human glioma is unclear. In this study, we detected the high expression of PP1γ and phosphorylated p65 (p-p65) in human glioma tissues. Besides, we demonstrated that upregulation of PP1γ was tightly related to poor 5-year survival via systemic statistical analysis. Employing serum-starved and re-feeding models of U251 and U87MG, we observed the increasing expression of PP1γ and p-p65 were accompanied by the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen (PCNA). Employing depletion-PP1γ models, we found downregulated PP1γ and p-p65 compared with upregulated IκBα, which indicates the inhibition of NF-κB pathway, and flow cytometry analysis confirmed the weakened cell proliferation. Moreover, we found that the translocation of p65 into the nucleus was impaired. Collectively, we identified the positive correlation between upregulation of PP1γ and human glioma cell proliferation and that knock-down of PP1γ alleviated the glioma proliferation by reducing p65 transportation into the nucleus. The results showed that PP1γ could accelerate human glioma proliferation via the NF-κB pathway.
Insights
High expression of Protein Phosphatase 1γ (PP1γ) correlates with poor glioma survival. Inhibiting PP1γ reduces glioma cell proliferation by blocking the NF-κB pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Protein Phosphatase 1γ (PP1γ) is crucial for cellular processes but its role in human glioma is unknown.
- PP1γ regulates diverse cellular functions including cell proliferation.
Purpose of the Study:
- To investigate the expression and function of PP1γ in human glioma.
- To determine the relationship between PP1γ, NF-κB pathway, and glioma cell proliferation.
Main Methods:
- Analysis of PP1γ and p-p65 expression in human glioma tissues.
- U251 and U87MG cell models (serum-starved/re-feeding, PP1γ depletion).
- Western blotting, flow cytometry, and statistical analysis.
Main Results:
- PP1γ and phosphorylated p65 (p-p65) were highly expressed in human glioma tissues.
- Upregulation of PP1γ correlated with poor 5-year survival and increased cell proliferation markers (cyclin D1, PCNA).
- PP1γ depletion inhibited NF-κB pathway activation, impaired p65 nuclear translocation, and reduced cell proliferation.
Conclusions:
- PP1γ upregulation is positively correlated with human glioma cell proliferation.
- PP1γ accelerates glioma proliferation by facilitating p65 nuclear translocation via the NF-κB pathway.
- PP1γ represents a potential therapeutic target for human glioma.
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