Background: Glioma has a poor prognosis, and is the most common primary and lethal primary malignant tumor in the central nervous system. Retinoic acid receptor-related orphan receptor A (RORA) is a member of the ROR subfamily of orphan receptors and plays an anti-tumor role in several cancers. Methods: A cell viability assay, the Edu assay, neurosphere formation assay, and xenograft experiments were used to detect the proliferative abilities of glioma cell line, glioma stem cells (GSCs). Western blotting, ELISAs, and luciferase reporter assays were used to detect the presence of possible microRNAs. Findings: Our study found for the first time that RORA was expressed at low levels in gliomas, and was associated with a good prognosis. RORA overexpression inhibited the proliferation and tumorigenesis of glioma cell lines and GSCs via inhibiting the TNF-a mediated NF-kB signaling pathway. In addition, microRNA-18a had a promoting effect on gliomas, and was the possible reason for low RORA expression in gliomas. Interpretation: RORA may be a promising therapeutic target in the treatment of gliomas.
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.
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