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PMID: 33907827 Published · ppublish English

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

International journal of molecular medicine ·Vol. 47 ·No. 6 ·2021-00-00

Xu T, Rao T, Yu WM, Ning JZ, Yu X, Zhu SM, Yang K, Bai T, Cheng F

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 主题词
Adaptor Proteins, Signal Transducing/genetics,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, Inbred BALB C Middle Aged Neoplasm Invasiveness PTEN Phosphohydrolase/antagonists & inhibitors,metabolism Phosphatidylinositol 3-Kinases/metabolism Prognosis Proto-Oncogene Proteins c-akt/metabolism Up-Regulation/genetics Urinary Bladder Neoplasms/genetics,pathology
Article Info
Journal
International journal of molecular medicine
Abbr.
Int J Mol Med
ISSN
1791-244X
Published
2021-00-00
Language
English
Country/Region
Greece
NLM ID
9810955
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