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 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.

Transcriptome Analysis of Diffuse Large B-Cell Lymphoma Cells Inducibly Expressing MyD88 L265P Mutation Identifies Upregulated CD44, LGALS3, NFKBIZ, and BATF as Downstream Targets of Oncogenic NF-κB Signaling

“…Depending on the context, the IκBζ protein can promote or inhibit gene expression and the activation of signaling pathways involved in producing inflammatory molecules [ 110 , 112 ]. Several studies have suggested that NFKBIZ may be a driver gene for the development and progression of certain types of cancer, including lymphoma [ 110 , 113 ]. High IκBζ expression was explicitly detected in ABC DLBCL [ 45 ].…”

Inflammation suppresses DLG2 expression decreasing inflammasome formation

“…This mutation is thought to affect the interactions with nuclear factor-κB complexes that bind to that region, altering the transcriptional regulation of its target genes and leading to cancer predisposition (Esteban-Jurado et al 2015). Furthermore, NFKBIZ has been shown to be downregulated in bladder cancer and to affect the PI3K/AKT/mTOR pathway to inhibit proliferation (Xu et al 2021). To test if DLG2 influenced these pathways we investigated the phosphorylation levels of AKT, FOXO3 and S6 in colon cancer cells.…”

Construction and verification of a novel hypoxia-related lncRNA signature related with survival outcomes and immune microenvironment of bladder urothelial carcinoma by weighted gene co-expression network analysis

“…The results from KEGG analysis indicated that MAPK, PI3K-Akt, and HIF-1 signaling pathways were markedly identified. MAPK and PI3K-Akt regulate tumor cell survival, proliferation, growth, mobility, and angiogenesis, whose activations were essential for BLCA metastasis and chemotherapy ( Xia et al, 2018 ; Sun et al, 2019 ; Lei et al, 2020 ; Ruan et al, 2020 ; Zhang et al, 2020 ; Xu et al, 2021a ; Kao et al, 2021 ). The HIF-1 signaling pathway was also discovered to be involved in hypoxic BLCA cell proliferation, migration, invasion, metastasis, and EMT, providing a rationale for clinical trials evaluating agents targeting this pathway ( Tickoo et al, 2011 ; Xue et al, 2014 ; Lu et al, 2020 ).…”