UBTD1 Drives Ovarian Cancer Progression and Chemoresistance via the TNF/AP-1 Signaling Axis

The ubiquitin domain-containing protein 1 (UBTD1), a protein involved in degradation and cell cycle regulation, is gaining recognition for its role in tumorigenesis. Ovarian cancer (OC) is the deadliest gynecological cancer, characterized by poor prognosis due to aggressive growth and chemoresistance. This study investigates the role of UBTD1 in OC pathogenesis. UBTD1 expression and prognosis were analyzed using public databases such as the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). UBTD1 was knocked down via Short hairpin RNA (shRNA) in A2780 and SKOV3 cells. Functional impacts on proliferation, migration, cell cycle, and apoptosis were assessed. RNA sequencing and Quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to investigate downstream pathways. UBTD1 is markedly overexpressed in OC and correlates with reduced survival. Its knockdown suppressed proliferation, migration, and invasion, induced G0/G1 arrest (upregulating p21, downregulating Cyclin D1), and enhanced cisplatin sensitivity. Transcriptome analysis revealed downregulation of the tumor necrosis factor (TNF) pathway and activator protein-1 (AP-1) factors FOS/FOSB. Ectopic FOS expression rescued the malignant phenotypes. UBTD1 drives OC progression and chemoresistance, potentially through the TNF/AP-1 axis, emerging as a prognostic biomarker and therapeutic target.