Abstract
Prostate cancer (PC) is polygenic disease involving many genes, and more importantly a host of gene-gene interactions, including transcriptional factors. The WSB1 gene is a transcriptional target of numerous oncoproteins, and its dysregulation can contribute to tumor progression by abnormal activation of targeted oncogenes. Using data from the Cancer Genome Atlas, we tested the possible involvement of WSB1 in PC progression. A multi-dimensional scaling (MDS) model was applied to clarify the association of WSB1 expression with other key genes, such as c-myc, ERG, Enhancer of Zeste 1 and 2 (EHZ1 and EZH2), WNT10a, and WNT 10b. An increased WSB1 expression was associated with higher PC grades and with a worse prognosis. It was also positively related to EZH1, EZH2, WNT10a, and WNT10b. Moreover, MDS showed the central role of WSB1 in influencing the other target genes by its central location on the map. Our study is the first to show a link between WSB1 expression and other genes involved in PC progression, suggesting a novel role for WSB1 in PC progression. This network between WSB1 and EZH2 through WNT/β-catenin may have an important role in PC progression, as suggested by the association between high WSB1 expression and unfavorable prognosis in our analysis.
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