UBR5, a potential diagnostic and prognostic biomarker induces osteosarcoma progression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) is located on chromosome 8q22, a region frequently altered in cancers.
• Emerging evidence suggests UBR5's involvement in cancer progression, but its specific roles in osteosarcoma are not well-defined.

Purpose of the Study:

• To investigate the expression, prognostic, and diagnostic value of UBR5 across various cancers, with a focus on osteosarcoma.
• To elucidate the oncogenic role of UBR5 in osteosarcoma progression and its potential as a therapeutic target.

Main Methods:

• Integrated analysis of TCGA, GTEx, and GEO databases for UBR5 expression and prognostic value.
• Utilized cBioPortal and GeneMANIA for genetic alterations and protein interactions.
• Validated UBR5 expression in osteosarcoma via immunohistochemistry, Western blotting, and immunofluorescence.
• Performed in vitro functional assays (gain/loss-of-function, CCK-8, colony formation, transwell) and in vivo tumor growth assessment in a mouse model.

Main Results:

• UBR5 expression is significantly elevated in osteosarcoma and multiple cancers, correlating with poor prognosis and high diagnostic accuracy.
• Frequent UBR5 alterations are linked to reduced overall survival, and protein analysis indicates involvement in chromatin assembly and histone modification.
• UBR5 knockdown inhibited osteosarcoma cell proliferation, migration, and invasion, while overexpression promoted these phenotypes; Ubr5 knockdown suppressed tumor growth in vivo.

Conclusions:

• UBR5 is identified as a key driver of osteosarcoma progression.
• UBR5 serves as a promising diagnostic and prognostic biomarker across various cancers.
• UBR5 represents a potential therapeutic target for cancer treatment.