UBR5, a potential diagnostic and prognostic biomarker induces osteosarcoma progression

Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) locates on chromosome 8q22, a region that commonly disrupted in a variety of cancers. Emerging evidence suggests UBR5 is involved in cancer progression, yet its oncogenic and prognostic roles, especially in osteosarcoma, remain poorly defined.

TCGA, GTEx, and GEO databases were integrated to analyze the expression level, and prognostic and diagnostic value of UBR5 across cancers. UBR5 genetic alterations and protein interactions were assessed using cBioPortal and GeneMANIA. UBR5 expression in osteosarcoma samples was validated by immunohistochemistry, Western blotting, and immunofluorescence staining. Functional assays, including gain- and loss-of-function experiments, CCK-8, colony formation, and transwell assays were used to evaluate the role of UBR5 in osteosarcoma cell lines. Additionally, the impact of Ubr5 knockdown on tumor growth was assessed in a mouse syngeneic transplant model.

UBR5 expression was significantly elevated in osteosarcoma and various cancers, and its upregulation was strongly associated with poor prognosis. Furthermore, UBR5 exhibited high diagnostic accuracy in distinguishing cancer from normal tissues. Genomic analysis revealed frequent UBR5 alterations correlated with poor overall survival (OS). Protein interaction analysis showed UBR5's association with chromatin assembly and histone modification. Knockdown of UBR5 inhibited proliferation, migration, invasion of osteosarcoma cell lines, while its overexpression promoted these malignant phenotypes in vitro. Moreover, knockdown of Ubr5 suppressed tumor growth in vivo.

This study identifies UBR5 as a key driver of osteosarcoma progression and a promising diagnostic and prognostic biomarker across cancers, highlighting its potential as a biomarker and therapeutic target.