Antioncogenic roles of USP9Y and DDX3Y in lung cancer: USP9Y stabilizes DDX3Y by preventing its degradation through deubiquitination

Abstract

In previous studies, downregulation of USP9Y and DDX3Y in lung cancer (LC) tissues was identified, while their function in LC progression remains elusive. In our current work, we intended to elucidate the effect and mechanisms of USP9Y and DDX3Y in LC. Gene downregulation has been confirmed in our LC tissues and cells. The effect of USP9Y or DDX3Y on LC cell malignancies was analyzed by functional assay. Both USP9Y and DDX3Y overexpression showed suppressive impact on LC cell malignancies. USP9Y overexpression has also been demonstrated to inhibit tumorigenesis in vivo. Based on GEPIA database, it was found that there was a positive correlation between the levels of USP9Y and DDX3Y in LC tissues. The mRNA expression of DDX3Y was not affected by USP9Y overexpression, while its protein levels were significantly up-regulated in USP9Y overexpressed LC cells. Moreover, USP9Y interacted with DDX3Y and has been demonstrated to stabilize DDX3Y expression by preventing its degradation via deubiquitination. In conclusion, USP9Y and DDX3Y exerted antioncogenic effects on the cell proliferation potential, cell cycle process, apoptosis, and tumorigenesis of LC. USP9Y binds to DDX3Y to prevent DDX3Y degradation through deubiquitination.