RESUMO
Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Due to its invasive nature, it cannot be thoroughly eliminated. WD repeat domain 12 (WDR12) processes the 32S precursor rRNA but cannot affect the synthesis of the 45S/47S primary transcript. In this study, we found that WDR12 is highly expressed in GBM according to the analysis results of mRNA expression by The Cancer Genome Atlas database. The high expression level of WDR12 is dramatically related to shorter overall survival and reduced disease-free survival. Next, we knocked down WDR12 and found that knockdown of WDR12 promoted the apoptosis and inhibited the proliferation by cell biology experiments. Differential expression genes in gene-chip revealed that WDR12 knockdown mainly inhibited cell cycle. Finally, we also found that WDR12 is associated with PLK1 and EZH2 in cell proliferation of GBM. Resumptively, this report showed a possible evidence that WDR12 drove malignant behavior of GBM, whose expression may present a neoteric independent prognostic biomarker in GBM.
Assuntos
Neoplasias Encefálicas/genética , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioblastoma/genética , Oncogenes/genética , Proteínas de Ligação a RNA/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Genômica/métodos , Glioblastoma/patologia , Humanos , Prognóstico , RNA Mensageiro/genéticaRESUMO
To investigate the effects of Ligustrazine, a compound derived from chuanxiong, on tumor necrosis factor-α (TNF-α) stimulated endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α in vitro. Nitric oxide (NO) was measured as a standard of endothelial dysfunction. Two important indicators of autoimmunity, intracellular adhesion molecular-1 (ICAM-1) and heat shock protein 60 (HSP60), were selected to evaluate the influence of Ligustrazine on HUVECs. Ligustrazine (40 µg/ml) significantly reversed the decrease in NO production induced by TNF-α (5 ng/ml) in HUVECs. The expressions of ICAM-1 and HSP60 were increased by TNF-α treatment, but dramatically inhibited by treatment with ligustrazine in TNF-α-stimulated cells. Ligustrazine increased the production of NO in HUVECs and had an immunomodulatory effect on HUVECs stimulated with TNF-α by down-regulating the expression of ICAM-1 and HSP60. These results suggest that ligustrazine protects the endothelium via inhibition of immunological reactions, preventing atherosclerosis.
