Deubiquitinating enzymes in breast cancer: in silico analysis of gene expression and metastatic correlation

Breast cancer, the most prevalent cancer in females, is a heterogeneous disease with various molecular subtypes, which presents challenges in diagnosis and treatment. Ubiquitination is one of the most critical post-translational protein modifications, that plays regulatory roles in numerous cellular processes including cell cycle progression, DNA replication & repair, apoptosis, transcription regulation, protein localization, trafficking and signal transduction. This modification can be reversed by deubiquitinases, or DUBs, a superfamily of cysteine proteases and metalloproteases that cleave ubiquitin-protein bonds. Dysregulation of DUBs has been associated to various diseases including cancer, making them promising targets for cancer therapy. We leveraged publicly available breast cancer datasets and employed various bioinformatics tools to identify differentially expressed DUBs in breast cancer. Our analysis identified six genes (COPS5, EIF3H, MINDY1, MINDY2, PSMD14 and USP26) with significant differential expression and survival implications. We further validated our findings experimentally and found upregulation of COPS5, EIF3H and MINDY 1 in MCF-7 and T47D breast cancer cell lines using qPCR analysis. To identify the role of these genes, EIF3H and COPS5, in disease progression, we constructed a protein-protein interaction (PPI) network with genes associated with metastasis and explored their correlation at the gene expression level in breast cancer patients. Together, this comprehensive study sheds light on DUB gene expression patterns in breast cancer with the potential to identify novel targets for therapeutic interventions.