Year: 2025
Type: article
Abstract: Objective: To comprehensively characterize the pan-cancer roles of Ubiquitin D (UBD/FAT10) in tumorigenesis, immune regulation, and therapeutic response through integrative multi-omics and expe+rimental analyses. Methods: Utilizing bulk RNA-seq (TCGA/GTEx/CPTAC), immune deconvolution, proteomics, and functional enrichment, we analyzed UBD expression, survival prognosis, immune infiltration, and molecular pathways across 33 cancers. Molecular docking and MD simulations were performed to assess UBD-protein interactions. Through lentivirus-mediated overexpression, functional assays (CCK-8, colony formation, wound healing, and Transwell), transcriptome sequencing, and biochemical validation, we demonstrated that UBD promotes malignant phenotypes in esophageal cancer via the TP53 signaling pathway. Results: UBD was upregulated in 14 cancers but downregulated in thyroid carcinoma (THCA) and kidney chromophobe (KICH). ROC analysis highlighted UBD's diagnostic potential (AUC >0.8 in gastrointestinal tumors). High UBD conferred protection in melanoma (SKCM, HR = 0.891) and sarcoma (SARC, HR = 0.899) but predicted poor outcomes in uveal melanoma (UVM, HR = 1.298) and pancreatic adenocarcinoma (PAAD, HR = 1.143).UBD positively correlated with the IFN-γ-dominant immune subtype (C2), characterized by CD8+ T cells/M1 macrophages. Drug sensitivity profiling nominated imatinib (Vina score: -8.9 kcal/mol) and TTNPB as potential therapies for UBD-high tumors, validated by stable MD simulations. In esophageal carcinoma (ESCA), UBD expression escalated with tumor stage and predicted poor survival (p<0.05).UBD enhances the proliferation and migration of esophageal cancer cells by modulating the TP53 signaling pathway, as validated through transcriptomic analysis and functional assays. Conclusions: This study advances UBD as a prognostic indicator and therapeutic target, bridging molecular insights with clinical translation in precision oncology.
Source: Frontiers in Oncology
Authors: Xu Zhang, Hongnian Pan, Xiuzhong Wang
Institutions: Anhui Medical University, Lu'an First People's Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: Anhui Medical University
OpenAlex ID: W4416404496