ABSTRACT: Background: ZNF25, a member of zinc finger proteins with KRAB domains family genes, is a transcription factor. Previous reports showed it is a biomarker of ovarian cancer. However, there are rarely reports about ZNF25 in other types of cancer, and its underlying mechanisms are not yet clear. Methods: Based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), IntOGen, TIMER, TIMER2, TISIDB, MethSurv, TISIDB, and Cistrome Data Browser (CDB) databases, we adopted bioinformatics methods to excavate the potential tumor genomic features of ZNF25, including dissecting the correlation with prognosis, gene mutation, immune cell infiltration, and DNA methylation in different tumors, and evaluated the association with tumor heterogeneity and stemness, and co-expression with Tex cells, chemokines chemokine receptors, and immunomodulators in pan-cancer. Additionally, we knocked down ZNF25 in U87-MG cells and performed RNA-seq analysis, then differential expression genes (DEGs) were further analyzed and visualized, like GO, and KEGG to interpret the biological significance. Results: The results show that ZNF25 has early diagnostic potential and was associated with the immune infiltration of different tumors. ZNF25 is associated with most tumor immune-infiltrating cells in pan-cancer, especially in glioma. Additionally, ZNF25 correlates with DNA methylation, tumor heterogeneity, Tex, and stemness in many types of cancers, like glioma. Besides, our findings demonstrate a close relationship between ZNF25 and mutated IDH1 in gliomas. Furthermore, our experiments showed that ZNF25 is involved in cancer pathways, mainly in PI3K-AKT and MAPK pathways.Conclusion: Through pan-cancer analysis combined with RNA-seq data, we discovered that ZNF25 might influence the progression of glioma mainly via the PI3K-AKT signaling pathway, and suggested that ZNF25 could serve as an indicator for tumor diagnosis, treatment, and prognosis across various types of tumors, including glioma.
