NFIB suppresses cell migration, invasion and EMT of bladder cancer through the PI3K-AKT signaling pathway.

NFIB, a pivotal transcription factor, intricately influences tumorigenesis by exerting dual roles as either an oncogenic promoter or a tumor-suppressive factor across a spectrum of tumor types. However, the specific impact of NFIB on bladder cancer remains poorly understood. This study aims to elucidate the biological function and molecular mechanism of NFIB in bladder cancer. We first found that the protein level of NFIB was downregulated in bladder cancer tissues compared to matched adjacent noncancerous tissues. Functional assays, including Wound healing and Transwell invasion assays, demonstrated that NFIB suppressed migration, invasion and epithelial-mesenchymal transition (EMT) of bladder cancer cells in vitro, wheras CCK8 assays showed NFIB had no significant effect on cell proliferation. In vivo experiments, including Xenograft and Nude mouse tail vein transfer assays, further supported these observations, indicating that NFIB inhibited lung metastasis of bladder cancer without affecting primary tumor growth. Finally, transcriptomic analysis confirmed that NFIB hindered the activation of the PI3K-AKT signaling pathway. Taken together, this study highlighted that NFIB serves as a tumor suppressor gene in bladder cancer, and suppresses cell migration, invasion and EMT through the modulation of the PI3K-AKT signaling pathway, revealing NFIB as a potential biomarker for monitoring early metastasis of bladder cancer and a target for therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-00900-4.