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NFKBIZ 的上调通过 PTEN/PI3K/Akt 信号通路影响膀胱癌的进展。

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

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Department of Urology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430060, P.R. China.

出版信息

Int J Mol Med. 2021 Jun;47(6). 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 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.

摘要

NF-κB 抑制剂 ζ(NFKBIZ)是 IκB 家族的一员,与 NF-κB 相互作用,已被报道是炎症、细胞增殖和存活的重要调节剂。然而,NFKBIZ 在膀胱癌(BC)中的作用尚不清楚。本研究旨在探讨 NFKBIZ 在 BC 中的功能。首先,使用 BC 组织样本、BC 细胞系和来自不同数据库的数据集,确定 NFKBIZ 的表达水平以及 NFKBIZ 表达与患者临床生存之间的关联。选择两种 BC 细胞系(T24 和 5637)过表达 NFKBIZ,并测定细胞的增殖、迁移和侵袭能力;此外,使用过表达 NFKBIZ 的 T24 细胞在小鼠模型中分析肿瘤生长情况。随后,使用数据库和临床及裸鼠肿瘤组织免疫组织化学分析的数据确定 NFKBIZ 与 PTEN 之间的关联。最后,使用 Western blot 评估 NFKBIZ、PTEN 和下游 PI3K/AKT/mTOR 信号通路之间的相互作用。综上所述,本研究结果表明,BC 中 NFKBIZ 表达较低,NFKBIZ 通过 PTEN/PI3K/Akt 信号通路抑制 BC 细胞的增殖,提示 NFKBIZ 可能是 BC 的一种新的预后生物标志物,并可能为 BC 提供潜在的治疗性肿瘤相关抗原。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/390d/8057294/9080fd263efd/IJMM-47-06-04942-g00.jpg

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