Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China; Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China.
Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China.
EBioMedicine. 2019 Oct;48:36-48. doi: 10.1016/j.ebiom.2019.09.037. Epub 2019 Oct 17.
Glioma is the most common primary malignant tumor in the central nervous system with frequent hypoxia and angiogenesis. Limb-Bud and Heart (LBH) is a highly conserved transcription cofactor that participates in embryonic development and tumorigenesis.
The conditioned media from LBH regulated human glioma cell lines and patient-derived glioma stem cells (GSCs) were used to treat the human brain microvessel endothelial cells (hBMECs). The function of LBH on angiogenesis were examined through methods of MTS assay, Edu assay, TUNEL assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.
Our study found for the first time that LBH was overexpressed in gliomas and was associated with a poor prognosis. LBH overexpression participated in the angiogenesis of gliomas via the vascular endothelial growth factor A (VEGFA)-mediated extracellular signal-regulated kinase (ERK) signalling pathway in human brain microvessel endothelial cells (hBMECs). Rapid proliferation of gliomas can lead to tissue hypoxia and hypoxia inducible factor-1 (HIF-1) activation, while HIF-1 can directly transcriptionally regulate the expression of LBH and result in a self-reinforcing cycle.
LBH may be a possible treatment target to break the vicious cycle in glioma treatment. : .
脑胶质瘤是中枢神经系统最常见的原发性恶性肿瘤，常伴有缺氧和血管生成。肢芽和心脏（LBH）是一种高度保守的转录共激活因子，参与胚胎发育和肿瘤发生。
LBH 调节的人胶质瘤细胞系和患者来源的胶质瘤干细胞（GSCs）的条件培养基用于处理人脑微血管内皮细胞（hBMECs）。通过 MTS 测定、Edu 测定、TUNEL 测定、Western blot 分析、qPCR 分析、荧光素酶报告基因测定和异种移植实验，研究 LBH 对血管生成的作用。
我们的研究首次发现 LBH 在脑胶质瘤中过度表达，并与不良预后相关。LBH 过表达通过血管内皮生长因子 A（VEGFA）介导的细胞外信号调节激酶（ERK）信号通路参与人脑微血管内皮细胞（hBMECs）的血管生成。胶质瘤的快速增殖可导致组织缺氧和缺氧诱导因子-1（HIF-1）激活，而 HIF-1 可直接转录调控 LBH 的表达，从而形成自我强化循环。
LBH 可能是一种治疗靶点，可打破胶质瘤治疗中的恶性循环。
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