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

Int J Mol Med. 2021 Jun;47(6):109. doi: 10.3892/ijmm.2021.4942. Epub 2021 Apr 28.

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 proliferation 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 downstream 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.

Keywords: NF‑κB inhibitor ζ; PTEN; bladder cancer; invasion; migration; proliferation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / antagonists & inhibitors
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Up-Regulation / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • NFKBIZ protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase

Grants and funding

The present study was supported by grants from the National Natural Science Foundation of China (grant. nos. 81870471 and 81800617) and the Science and Technology Major Project of Hubei Province (grant. no. 2019AEA170).