IKBKE 通过调节血管内皮生长因子的表达和分泌来调控神经胶质瘤中的血管生成。

IKBKE regulates angiogenesis by modulating VEGF expression and secretion in glioblastoma.

机构信息

Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China.

Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China.

出版信息

Tissue Cell. 2023 Oct;84:102180. doi: 10.1016/j.tice.2023.102180. Epub 2023 Jul 23.

DOI:10.1016/j.tice.2023.102180

PMID:37573607

Abstract

PURPOSE

As a noncanonical inflammatory kinase, IKBKE is frequently overexpressed and activated and has been identified as an oncogenic protein in glioblastoma. However, the potential function and underlying mechanism of IKBKE contributing to tumor angiogenesis remain elusive.

METHODS

First, we analyzed the correlation between IKBKE and VEGF expression in glioma samples by immunohistochemistry (IHC). Second, HUVEC-related assays and Western blot were used to detect the regulatory effect of IKBKE on angiogenesis by modulating VEGF expression. Third, IKBKE depletion could alleviate the influence of VEGF expression on IHC of intracranial glioma model.

RESULTS

We demonstrate that depletion of IKBKE markedly inhibits tumor growth and angiogenesis in glioblastoma. Mechanistically, IKBKE induces VEGF expression and secretion by regulating AKT/FOXO3a in glioblastoma.

CONCLUSIONS

This study reveals that IKBKE is a novel oncogenic molecule that induces angiogenesis through the promotion of VEGF expression and highlights the potential of targeting IKBKE for glioblastoma therapy.

摘要

目的

作为一种非典型炎性激酶，IKBKE 常过度表达和激活，并已被鉴定为神经胶质瘤中的致癌蛋白。然而，IKBKE 促进肿瘤血管生成的潜在功能和潜在机制仍不清楚。

方法

首先，我们通过免疫组织化学（IHC）分析了神经胶质瘤样本中 IKBKE 与 VEGF 表达之间的相关性。其次，通过调节 VEGF 表达，使用 HUVEC 相关测定和 Western blot 检测 IKBKE 对血管生成的调节作用。第三，IKBKE 耗竭可减轻 VEGF 表达对颅内神经胶质瘤模型 IHC 的影响。