Upregulation of NFKBIZ affects bladder cancer progression via the PTEN/PI3K/Akt signaling pathway

Abstract

NF-κB inhibitor ζ (NFKBIZ), a member of the IκB family that interacts with NF-κB, has been reported to be an important regulator of inflammation, cell prolifera- tion and survival. However, the role of NFKBIZ in bladder cancer (Bc) remains unknown. The present study aimed to investigate the functions of NFKBIZ in Bc. First, the expression levels of NFKBIZ and the associations between NFKBIZ expression and the clinical survival of patients were determined using Bc tissue samples, Bc cell lines and datasets from different databases. Two Bc cell lines (T24 and 5637) were selected to overexpress NFKBIZ, and the proliferative, migratory and invasive abilities of cells were determined; additionally, tumor growth following transplantation in in vivo mouse models was analyzed using T24 cells overexpressing NFKBIZ. Subsequently, the association between NFKBIZ and PTEN was determined using data from databases and immunohistochemistry analysis of clinical and nude mice tumor tissues. Finally, the interactions between NFKBIZ, PTEN and the down- stream PI3K/AKT/mTOR signaling pathway were evaluated using western blotting. In conclusion, the present results indicated that NFKBIZ expression was low in Bc, and NFKBIZ inhibited the proliferation of Bc cells through the PTEN/PI3K/Akt signaling pathway, suggesting that NFKBIZ may represent a novel prognostic biomarker in Bc and may provide a potential therapeutic tumor-associated antigen for Bc.