ZNF25 as an immunotherapy target: pan-cancer biomarker potential and mechanistic exploration in glioma

Background ZNF25 , a KRAB domain-containing zinc finger transcription factor, has been identified as a potential biomarker in ovarian cancer. However, its pan-cancer significance and the underlying molecular mechanisms in other malignancies remain largely unclear. Methods We performed a systematic pan-cancer analysis of ZNF25 using TCGA and GTEx databases, integrated with platforms including cBioPortal, TISIDB, TIMER, and Sangerbox. Associations between ZNF25 expression and clinical outcomes, genomic alterations, immune cell infiltration, and DNA methylation were systematically evaluated. Based on these findings, functional validation was performed in glioma cell lines (U87-MG and A172) via siRNA-mediated knockdown of ZNF25 , followed by cell viability assays, wound healing assays, and Western blot assays. Additionally, RNA-seq was conducted in ZNF25 - knockdown U87-MG cells to identify differential expression genes and enriched pathways. Results ZNF25 exhibited significant associations with diagnostic potential, poor prognosis, and immune infiltration across multiple cancer types, with the most pronounced effects observed in glioma. Functional assays demonstrated that ZNF25 knockdown suppressed the proliferation and migration of glioma cells. Transcriptomic and biochemical analysis indicated that ZNF25 promotes glioma progression, at least in part, through the positive modulation of the PI3K-AKT pathway. Conclusions Collectively, our findings identify ZNF25 as a potential diagnostic and prognostic biomarker across various cancers and suggest its critical role in glioma progression. This study provides new insights into the functional role of ZNF25 and highlights its potential as a therapeutic target, particularly in glioma.