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Published on: October 20, 2016
ZNF395 facilitates macrophage polarization and impacts the prognosis of glioma
Feng Xiao1, Jie Shen2, Lihui Zhou2
1Department of Neurosurgery, The 1st Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, Zhejiang, China.
Abstract:
The immune microenvironment of glioma attributes to the initiation and development of glioma; however, the underlying mechanisms of tumor microenvironment formation have not been fully understood. In this study, we revealed that Zinc Finger Protein 395 (ZNF395), a member of the Kruppel C2H2-type zinc-finger protein family and also known as a common transcription factor, was aberrantly overexpressed in glioma and positively associated with the poor clinicopathological features and the prognosis of patients with glioma based on the analyses of TCGA, CGGA and other datasets. Further in vitro experimental data demonstrated that the upregulation of ZNF395 promoted the proliferation of glioma cells. In addition, functional enrichment analysis showed that ZNF395 was involved in immune processes and correlated with macrophage infiltration and polarization. Moreover, C-C Motif Chemokine Ligand 20 (CCL20), one of the ZNF395 co-expressed genes, was validated as the downstream factor under the transcriptional regulation of ZNF395. Importantly, cell co-culture experiments confirmed that ZNF395 upregulated both the intracellular and secreted CCL20 level of glioma cells and induced M2 macrophage polarization which is known to promote the malignant progression of glioma. Taken together, our findings suggested that ZNF395 might play an essential role in glioma development, and inhibition of ZNF395 might be a plausible strategy for glioma therapy.
Insights
Zinc Finger Protein 395 (ZNF395) is overexpressed in glioma, promoting tumor cell proliferation and M2 macrophage polarization via CCL20. Inhibiting ZNF395 may offer a new glioma therapy strategy.
Area of Science:
- Neuro-oncology
- Cancer immunology
- Molecular biology
Background:
- The tumor microenvironment significantly influences glioma development.
- Understanding glioma's immune microenvironment mechanisms is crucial for effective therapy.
Purpose of the Study:
- To investigate the role of Zinc Finger Protein 395 (ZNF395) in glioma.
- To elucidate the molecular mechanisms by which ZNF395 affects glioma progression and immune infiltration.
Main Methods:
- Analysis of patient datasets (TCGA, CGGA) to assess ZNF395 expression and correlation with clinical features.
- In vitro experiments to evaluate ZNF395's effect on glioma cell proliferation.
- Functional enrichment analysis to identify ZNF395-associated biological processes.
- Validation of C-C Motif Chemokine Ligand 20 (CCL20) as a downstream target of ZNF395.
- Co-culture experiments to assess ZNF395's impact on macrophage polarization.
Main Results:
- ZNF395 was found to be aberrantly overexpressed in glioma, correlating with poor prognosis.
- ZNF395 overexpression promoted glioma cell proliferation in vitro.
- ZNF395 was linked to immune processes, macrophage infiltration, and polarization.
- CCL20 was identified as a direct transcriptional target of ZNF395.
- ZNF395 upregulated CCL20 in glioma cells, inducing M2 macrophage polarization.
Conclusions:
- ZNF395 plays a significant role in glioma development and progression.
- ZNF395 influences the glioma immune microenvironment by promoting M2 macrophage polarization through CCL20.
- Targeting ZNF395 presents a potential therapeutic strategy for glioma.
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