Unraveling the secrets of UBE2S in endometrial cancer: Potential targets for diagnosis, prognostic assessment, and ferroptosis therapy

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doi:10.1016/j.cellsig.2025.112325

UBE2S exhibits elevated expression in various cancers. Its overexpression is positively correlated with poor prognosis in endometrial cancer (UCEC) patients. However, the role and underlying mechanisms of UBE2S in UCEC progression remain to be fully elucidated. Utilizing TCGA data, we initially identified UBE2S as a prognostically significant gene. Subsequently, We evaluated UBE2S expression levels in UCEC tumor tissues and cell lines using immunohistochemistry (IHC), qRT-PCR and Western blotting. Following shRNA-mediated knockdown of UBE2S, we systematically assessed its effects on cell proliferation and migration through CCK-8, EdU staining, colony formation, wound healing, and Transwell migration assays. These findings were further validated through in vivo experiments. RNA sequencing (RNA-seq) and TCGA data analysis revealed the cellular biological functions mediated by UBE2S. Flow cytometry and FerroOrange staining were used to examine the effects of UBE2S knockdown on the cell cycle, apoptosis, and ferroptosis. Western blotting was utilized to confirm changes in the expression of proteins associated with these pathways. A prediction model based on five core UBE2-genes demonstrated significant prognostic value. Notably, UBE2S exhibited significantly elevated expression in UCEC tissues, which was strongly correlated with adverse prognosis and tumor immunosuppressive microenvironment. Additionally, UBE2S knockdown resulted in the suppression of malignant phenotypes in UCEC cells, characterized by reduced cell proliferation and migration both in vitro and in vivo. Furthermore, downregulation of UBE2S induced cell cycle arrest, enhanced apoptosis, and increased ferroptosis. As a potential oncogene and therapeutic target in UCEC, UBE2S may play a critical role in UCEC cell malignancies.

Unraveling the secrets of UBE2S in endometrial cancer: Potential targets for diagnosis, prognostic assessment, and ferroptosis therapy

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