Abstract

Aims The UBE2D family plays essential roles in protein degradation and cell cycle regulation and has been implicated in cancer. However, the specific function of UBE2D4 in glioma and its clinical and biological significance remain unclear. This study aimed to investigate the expression pattern, regulatory mechanism, and functional role of UBE2D4 in glioma progression. Materials and methods Transcriptomic data from TCGA, GTEx, and GEO databases were analyzed to evaluate UBE2D4 expression and its association with patient prognosis. Bioinformatics analyses and experimental assays were used to explore the transcriptional regulation of UBE2D4 by YY1. Gain- and loss-of-function experiments were conducted to assess the effects of UBE2D4 on glioma cell proliferation, migration, invasion, and cell cycle progression in vitro and in vivo . The interaction between UBE2D4 and p53 and its impact on p53 stability were also examined. Key findings UBE2D4 expression was significantly upregulated in glioma and correlated with poor patient survival. YY1 was identified as a key transcriptional regulator that enhanced UBE2D4 expression by binding to its promoter. Silencing UBE2D4 inhibited glioma cell proliferation, migration, and invasion, induced G2/M cell cycle arrest, and stabilized p53 by suppressing its degradation. Significance These findings demonstrate that UBE2D4 promotes glioma progression through YY1-mediated transcriptional activation, acceleration of cell cycle progression, and inhibition of p53-dependent tumor suppression. UBE2D4 may serve as a potential prognostic biomarker and therapeutic target for glioma.