TNFRSF11B is involved in the development and progression of various malignancies. However, its function in bladder cancer and its associated carcinogenic mechanisms are less well understood. Here, researchers evaluated the clinical significance of TNFRSF11B in bladder cancer and its associated signaling pathways through bioinformatics analysis. The expression levels of TNFRSF11B were measured in bladder tissue and bladder cancer cells. To investigate the effect of the PI3K/AKT pathway on TNFRSF11B, experiments were performed using the PI3K/AKT inhibitor LY294002. The results showed that TNFRSF11B was significantly upregulated in bladder cancer tissue and various bladder cancer cell lines. Inhibition of TNFRSF11B expression inhibited the proliferation, migration, and invasion of bladder cancer cells. Overexpression of TNFRSF11B, however, had the opposite effect. These findings were further confirmed by in vivo experiments. Furthermore, TNFRSF11B promotes the malignant progression of bladder cancer by regulating the PI3K/AKT pathway. In summary, TNFRSF11B is highly expressed in bladder cancer and plays an important role in promoting cancer through the PI3K/AKT pathway. Therefore, TNFRSF11B may become a potential prognostic marker for bladder cancer treatment.
To validate the mechanism by which TNFRSF11B promotes tumorigenesis through the PI3K/AKT pathway, researchers conducted rescue experiments to confirm its pro-proliferative effect on bladder cancer cells. TNFRSF11B-overexpressing cells were treated with the PI3K/AKT inhibitor LY294002. CCK-8 and LDH assays showed that LY294002 significantly reduced the cell viability of TNFRSF11B-overexpressing T24 and 5637 cells (Figure 1A and B). Transwell invasion and migration assays demonstrated that LY294002 significantly inhibited the invasion and migration of TNFRSF11B-overexpressing T24 and 5637 cells (Figure 1C and D). Wound healing assay further confirmed that LY294002 inhibited the migration of bladder cancer cells (Figure 1E). Furthermore, researchers investigated whether TNFRSF11B exerts its oncogenic effects by inhibiting apoptosis. Flow cytometry results showed that LY294002 reversed the inhibitory effect of TNFRSF11B overexpression on cell apoptosis. Therefore, TNFRSF11B promotes tumor progression by inhibiting apoptosis in bladder cancer cells.
Figure 1. LY294002 inhibits the cancer-promoting activity of TNFRSF11B via the PI3K/AKT pathway. (Deng H, et al., 2024)