ZNF395 facilitates macrophage polarization and impacts the prognosis of glioma

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.