Impact of G-CSF on expressions of Egr-1 and VEGF in acute ischemic cerebral injury.

The aim of the present study was to investigate the protective effect of granulocyte colony-stimulating factor (G-CSF) on acute ischemic cerebral injury, and its mechanism through the impact of G-CSF on early growth response-1 (Egr-1) and vascular endothelial growth factor (VEGF) expressions. Male Sprague-Dawley (SD) rats were divided them into three groups, i.e., the sham, model and G-CSF groups to measure the effect of G-CSF on the volume of cerebral infarction and level of lactate dehydrogenase (LDH) in rats. Hematoxylin and eosin (H&E) staining method was performed for histopathological examination. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the mRNA and protein expressions of Egr-1 and VEGF in different groups. Furthermore, Statistical Product and Service Solutions (SPSS) 17.0 software was applied to detect the differences in the expression of Egr-1 and VEGF between the two groups. Compared with the sham group, we found that the volume of cerebral infarction and LDH content in the model group were significantly elevated. By contrast, in the model group, those indicators in the G-CSF group were obviously decreased. H&E staining results also showed that G-CSF could decrease the necrotic area in cerebral infarction and the incidence of inflammation, and sustain the integrity of the molecular structure. Immunofluorescence staining results revealed that the protein expressions of Egr-1 and VEGF in the model group were all significantly decreased, while those in the G-CSF group were remarkably elevated. RT-PCR and western blot analysis revealed that the mRNA and protein expressions of Egr-1 and VEGF in the model group were decreased obviously, but those in the G-CSF group were elevated significantly, and the differences between the two groups showed statistical significance (P<0.05). G-CSF manifests a significant protective effect on the acute ischemic cerebral injury, which may be realized through its effect on the expressions of Egr-1 and VEGF.

Overexpression of p53 delivered using recombinant NDV induces apoptosis in glioma cells by regulating the apoptotic signaling pathway.

Malignant glioma is the most common primary brain carcinoma in the world and has a poor survival rate. Previous studies have demonstrated that p53 dysfunction contributes to the development and severity of malignant glioma. It has also been demonstrated that Newcastle disease virus (NDV) may be a viable candidate for the treatment of various types of cancer. In the present study, a p53 oncolytic agent delivered using recombinant NDV (rNDV-p53) was constructed and its anti-tumor effects in vitro and in vivo were assessed. Glioma cell lines and a xenograft mouse model were utilized to assess the ability of p53 and rNDV to promote apoptosis and induce immunotherapy, respectively. The mechanism of rNDV-p53 in glioma therapy was investigated using quantitative polymerase chain reaction and immunohistochemistry. Tumor-specific cytotoxic T-lymphocyte (CTL) responses and lymphocyte infiltration were also analyzed in glioma-bearing models. The results of the present study demonstrate that rNDV-p53 may be a potential therapeutic agent that improves the prognosis of mice with glioma. It was revealed that rNDV-p53 inhibits glioma cell growth and aggressiveness in vitro and in vivo compared with rNDV and p53 alone. The results also demonstrated that rNDV-p53 induced glioma cell apoptosis by upregulating apoptosis-related genes. In addition, the present study demonstrated that rNDV-p53 significantly stimulated CTL responses and lymphocyte infiltration whilst increasing the number of apoptotic bodies in vivo. Furthermore, rNDV-p53 therapy inhibited tumor regression and prolonged the survival of glioma-bearing mice. In conclusion, rNDV-p53 invoked an immune response against glioma cells, which may serve as a comprehensive immunotherapeutic schedule for glioma.

lncRNA CCAT1 Promotes Glioma Tumorigenesis by Sponging miR-181b.

Colon cancer-associated transcript 1 (CCAT1), a long non-coding RNA (lncRNA), is upregulated and has a vital role in the pathogenesis of numerous cancers. Recently, its high expression was found in glioma tissues. miR-181b is downregulated in glioma and acts as a tumor suppressor. However, the exact mechanism of CCAT1 action in the regulation of glioma development remains unknown. CCAT1 and miR-181b expression was firstly examined in glioma tissue samples by real-time PCR. An RNA interference approach was used to downregulate CCAT1 expression and we analyzed the underlying mechanism of CCAT1 by using bioinformatics analysis, CCK-8 assay, Transwell assay, flow cytometry, luciferase assay, RNA immunoprecipitation, real-time PCR, Western blot, and xenograft models. CCAT1 expression was significantly increased, while miR-181b decreased, in glioma tissues. Interestingly, miR-181b expression was negatively correlated with the CCAT1 level in glioma samples. Knockdown of CCAT1 notably suppressed proliferation, migration and the epithelial-mesenchymal transition (EMT) process, and promoted the apoptosis of U87 and LN229 glioma cells, which could be enhanced by transfection with miR-181b mimic while it was abolished by anti-miR-181b. Additionally, we found that CCAT1 may act as a competing endogenous RNA (ceRNA) for miR-181b, regulating the de-repression of FGFR3 and PDGFRα. In conclusion, CCAT1 promotes glioma tumorigenesis by sponging miR-181b, leading to the de-repression of its endogenous targets FGFR3 and PDGFRα, which provides a potential therapeutic target for glioma treatment. J. Cell. Biochem. 118: 4548-4557, 2017. © 2017 Wiley Periodicals, Inc.