Work

Pharmacological inhibition of BUB1 suppresses UCEC progression by modulating the PI3K-AKT pathway and reversing anoikis resistance and immune evasion: a multi-omics and experimental study

Year: 2026

Type: article

Abstract: Background Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecological malignancy with poor prognosis and limited therapeutic strategies. The mitotic checkpoint kinase BUB1 has emerged as a potential regulator of tumor progression, but its clinical and functional roles in UCEC remain unclear. Methods Transcriptomic datasets from TCGA and GEO were analyzed to evaluate BUB1 expression, survival impact, pathway enrichment, methylation, and immune infiltration. Protein–protein interactions and drug sensitivity analyses were performed using bioinformatics pipelines. Functional validation was conducted in HEC-1-B cells treated with the BUB1 inhibitor 2OH-BNPP1 using MTT, wound healing, and qPCR assays. Results BUB1 was significantly upregulated in UCEC tumors compared with normal endometrium, associated with advanced disease stage and reduced overall survival, confirming its role as an unfavorable prognostic biomarker. Enrichment analyses linked BUB1 to cell cycle regulation, PI3K-AKT signaling, and anoikis resistance. BUB1 expression positively correlated with infiltration of macrophages, neutrophils, and CD4⁺ T cells. Pharmacological inhibition with 2OH-BNPP1 reduced cell viability, impaired migration, and suppressed BUB1 expression in a dose-dependent manner, supporting its oncogenic role in endometrial carcinoma. Conclusion This study identifies BUB1 as a clinically relevant prognostic biomarker and therapeutic target in UCEC. Targeting BUB1 interrupts tumor-promoting processes including proliferation, survival, and migration, underscoring its translational potential for future therapeutic development.

Source: Future Journal of Pharmaceutical Sciences

DOI: 10.1186/s43094-026-01017-3