Fig. 8: WFDC21P is required for Csn-B-inhibited HCC cell proliferation.

a Csn-B increases WFDC21P expression levels in a dose dependent manner in Huh7 and HepG2 cells. The WFDC21P expression levels were detected by RT-qPCR. b Csn-B increases the activity of the WFDC21P promoter. Luciferase assays were performed in Huh7 cells. c Csn-B inhibits the HCC cell viability. MTT assays were performed in Huh7 and HepG2 cells. d Csn-B cannot inhibit cell viability in WFDC21P knockdown cells. MTT assays were performed in Huh7 and HepG2 cells. e WFDC21P is required for the inhibitory effect of Csn-B in xenograft tumors (n = 6). The tumor growth curves, tumor weights, and Ki-67 expression levels are shown. Scale bars in xenograft images and Ki-67 staining were 1 cm and 100 μm, respectively. f Schematic diagram of the Nur77–WFDC21P–PFKP/PKM2 axis in HCC progression inhibition. Csn-B, an agonist for Nur77, stimulates the transcriptional activity of Nur77. Nur77 then activates the transcription of WFDC21P by directly binding to NBREs on the promoter of WFDC21P. On the one hand, WFDC21P interacts with PFKP to attenuate its tetramer formation, resulting in decreased PFKP activity. On the other hand, WFDC21P interacts with PKM2, which blocks its nuclear translocation and, therefore, its function as a transcriptional coactivator. As a result, WFDC21P inhibits glycolysis in HCC cells and suppresses HCC development. *p < 0.05; **p < 0.01; ***p < 0.001 and ns no significance.