GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth

The WD repeat domain 77 (WDR77) protein plays a critical role in prostate development and dysregulation of WDR77 expression is associated with prostate tumorigenesis. This study investigated the regulatory effects of GATA3 and E2F6 on WDR77 gene expression. A negative correlation between GATA3/E2F6 and WDR77 expression at both mRNA and protein levels was observed during prostate development and prostate tumorigenesis. Prostate cancer cells lost expression of GATA3 and E2F6 and re-expression of GATA3 and E2F6 resulted in a dose-dependent reduction in WDR77 expression and cell growth. Exogenous expression of WDR77 relieved the growth inhibition by GATA3. GATA3 and E2F6 directly interact with the promoter of the WDR77 gene in vitro and in vivo and repress WDR77 promoter activity. These results provide valuable insights into the molecular mechanisms governing WDR77 expression during prostate development and prostate tumorigenesis.