Fig. 7. Reduced DDX5 protein levels in human HCCs associated with increased nuclear NFKB2/p52.
A Immunohistochemistry (IHC) of human HCCs from tissue microarray (TMA) referenced in [7], using DDX5 and NFKB2/p52 antibodies. The numbers above each image indicate the tumor position in TMA (Supplementary Fig. S4). Representative images at 20X magnification. B Immunoblot of lysates from WT and DDX5KO cells using the indicated antibodies. Histone 3 is loading control for nuclear lysates. C Diagram illustrates the interconnected pathways activated by DDX5 downregulation. Specifically, decreased levels of DDX5 lead to activation of Wnt/β-catenin signaling by inducing DVL1, resulting in transcriptional upregulation of NIK and subsequent activation of non-canonical NF-κB (p52/RelB). This activation leads to transcriptional induction of NRF2. Additionally, DX5 deficiency stabilizes p62/SQSTM1, leading to proteasomal degradation of KEAP1, thus enhancing NRF2 stabilization.