Overexpression of Limb-Bud and Heart (LBH) promotes angiogenesis in human glioma via VEGFA-mediated ERK signalling under hypoxia
Yang Jiang,
Jinpeng Zhou,
Dan Zou,
Dianqi Hou,
Haiying Zhang,
Junshuang Zhao,
Long Li,
Jiangfeng Hu,
Ye Zhang,
Zhitao Jing
Affiliations
Yang Jiang
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
Jinpeng Zhou
Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China
Dan Zou
The First Laboratory of Cancer Institute, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China
Dianqi Hou
Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China
Haiying Zhang
International Education College, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshan East Road, Shenyang, Liaoning 110042, China
Junshuang Zhao
Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China
Long Li
Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China
Jiangfeng Hu
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China
Ye Zhang
The First Laboratory of Cancer Institute, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China; Corresponding authors.
Zhitao Jing
Department of Neurosurgery, the First Hospital of China Medical University, No. 155, North Nanjing Street, Shenyang, Liaoning 110001, China; Corresponding authors.
Background: 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. Methods: 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. Findings: 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. Interpretation: LBH may be a possible treatment target to break the vicious cycle in glioma treatment. : Keywords: Glioma, Glioma stem cells, LLimb-Bud and Heart, Angiogenesis, ERK signalling pathway
