2. Academic Validation
  3. UBE2D4 transcriptionally activated by YY1 drives G2/M progression through enhancing MDM2-dependent p53 degradation in glioma

UBE2D4 transcriptionally activated by YY1 drives G2/M progression through enhancing MDM2-dependent p53 degradation in glioma

  • Life Sci. 2026 Apr 15:391:124275. doi: 10.1016/j.lfs.2026.124275.
Dian Liu 1,  Keqin Zhang 2,  Xiang Xiao 3,  Jie Liu 4,  Jia You 5
Affiliations

Affiliations

  • 1 Department of Lymphoma and Abdominal Radiotherapy, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, PR China.
  • 2 Department of Nuclear Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, PR China.
  • 3 Department of Neurosurgery, Xiangya Hospital, Central South University, Jiangxi (National Regional Center for Neurological Disease), Nanchang, 330006, Jiangxi, PR China; Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, Jiangxi, PR China.
  • 4 Department of Pathology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, Hunan, PR China.
  • 5 Department of Neurosurgery, Xiangya Hospital, Central South University, Jiangxi (National Regional Center for Neurological Disease), Nanchang, 330006, Jiangxi, PR China; National Clinical Research Center of Geriatric Disorders (Xiangya Hospital), Central South University, Changsha, 410008, Hunan, PR China. Electronic address: [email protected].
PMID: 41713576 DOI: 10.1016/j.lfs.2026.124275
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.

Keywords

Cell cycle; Glioma; Transcription regulation; UBE2D4; YY1; p53 degradation.

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