Fig. 7
Oncogenic effect of DDX27 is dependent on NPM1-mediatd activation of NF-кB signaling. a and b Transfection with control-siRNA (siCTL) or specific NPM1-siRNA (siNPM1) in the control and DDX27-overexpressing HCT116 (or SW480 cells) revealed that silencing of NPM1 abolished growth advantage conferred by ectopic expression of DDX27. The cell lysates were blotted with indicated antibody. c and d HCT116 or SW480 cells were treated with 50 ng/ml TNF-α for indicated time. Silencing of NPM1 abolished DDX27-enhaced activation of NF-кB luciferase activity. e HCT116 cells were treated with 50 ng/ml TNF-α for 3 h. The mRNA expression of NF-кB target genes (BIRC3, CXCL3, TNF, and TNFAIP3) were measured by qPCR. f Proposed mechanistic scheme of DDX27. DDX27 directly interacts with NPM1 and promotes its interaction with p65 in the nucleus, hence increased the binding activity of p65 to promoters of NF-кB target genes and enhanced the transcription. DDX27 likely mediates a positive autocrine feedback on NF-κB. Enhanced NF-кB signaling will increase cell proliferation, inhibit apoptosis and promote metastasis for colorectal tumorigenesis. (*P < 0.05; **P < 0.01; ***P < 0.001)
