Overexpression of Limb-Bud and Heart (LBH) Promotes Angiogenesis in Human Glioma via VEGFA-mediated ERK Signaling Under Hypoxia

Autor: Jiangfeng Hu, Haiying Zhang, Jinpeng Zhou, Junshuang Zhao, Dianqi Hou, Long Li, Yang Jiang, Dan Zou, Zhitao Jing, Ye Zhang
Rok vydání: 2019
Předmět:
0301 basic medicine
Vascular Endothelial Growth Factor A
MAPK/ERK pathway
Angiogenesis
Gene Expression
lcsh:Medicine
Biology
medicine.disease_cause
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Mice
0302 clinical medicine
Cell Line
Tumor
Glioma
Animals
Humans
Medicine
Extracellular Signal-Regulated MAP Kinases
Hypoxia
Microvessel
Neoplasm Staging
lcsh:R5-920
Neovascularization
Pathologic
business.industry
lcsh:R
General Medicine
medicine.disease
Immunohistochemistry
Hedgehog signaling pathway
Disease Models
Animal
Vascular endothelial growth factor A
030104 developmental biology
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Commentary
Cancer research
Heterografts
Female
Neoplasm Grading
Stem cell
Signal transduction
lcsh:Medicine (General)
business
Carcinogenesis
Signal Transduction
Transcription Factors
Zdroj: EBioMedicine, Vol 48, Iss, Pp 36-48 (2019)
EBioMedicine
ISSN: 1556-5068
DOI: 10.2139/ssrn.3436247
Popis: 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) signaling 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. Funding Statement: This work was funded by National Natural Science Foundation of China (No. 81101917, 81270036, 30901736), the Plan to Focus on Research and Development from Science and Technology project of Liaoning Province (No. 2017225029), Natural Science Foundation of Liaoning Province (No. 20170541022), Science and Technology Plan Project of Shenyang City (No. 18-014-4-11), and Fund for Scientific Research of The First Hospital of China Medical University (No. FHCMU- FSR), and Shanghai Sailing Program (No. 19YF1439000). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of China Medical University and written informed consent was obtained from all patients.
Databáze: OpenAIRE
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