Overexpression of Limb-Bud and Heart (LBH) promotes angiogenesis in human glioma via VEGFA-mediated ERK signalling under hypoxia

摘要

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.