RESUMEN
BACKGROUND: Glioblastoma is a brain malignant tumor grade IV, highly invasive. Alterations in several signaling pathways are involved in glioblastoma development. In this work, we evaluated the IFN-γ canonical signaling pathway in glioblastoma cells and its effect on cell viability and migration. METHODS: The levels of STAT1/pSTAT1, IRF1, and PD-L1 in LN-18 glioblastoma cells were analyzed using western blotting. Cell viability was evaluated by calcein-AM/propidium iodide assays, and a wound healing assay was used to study the migration of glioblastoma cells treated with IFN-γ. Our aim was to determine the expression of IFN-γ signaling elements in cell lines and tissue from glioblastoma samples and examine the relationship between these elements and the survival of glioblastoma patients. The following platforms were utilized for analysis: the CCLE (Cancer Cell Line Encyclopedia), UALCAN (University of Alabama at Birmingham Cancer data analysis Portal), GEPIA (Gene Expression Profiling Interactive Analysis), and GENT2 (Gene Expression patterns across Normal and Tumor tissues). RESULTS: Our results evidenced that IFN-γ signaling increases non-phosphorylated and phosphorylated STAT1 levels and promotes the upregulation of IRF1 and PD-L1 in glioblastoma cells. The activation of IFN-γ signaling increased cell migration without affecting the viability of glioblastoma cells. Furthermore, in silico analysis showed that the elements of IFN-γ signaling pathways (IFNGR1/IFNGR2/STAT1/IRF1) are upregulated in human glioblastoma samples. The upregulation of IFN-γ signaling was associated with shorter survival in glioblastoma patients. CONCLUSION: IFN-γ signaling pathway is upregulated in glioblastoma, displaying pro-tumor activity. Thus, IFN-γ signaling elements may be potential biomarkers and targets for treating glioblastoma.
Asunto(s)
Glioblastoma , Interferón gamma , Humanos , Interferón gamma/metabolismo , Glioblastoma/genética , Antígeno B7-H1/metabolismo , Regulación hacia Arriba , Transducción de Señal , Línea Celular TumoralRESUMEN
The bovine viral diarrhea virus (BVDV-1) is a pathogen with the capacity to modulate the interferon type I system. To further investigate the effects of BVDV-1 on the production of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the IFNbeta expression profiles were analyzed. The results showed that cpBVDV-1 was able to induce the production of IFNbeta in a way similar to polyinosinic-polycytidylic acid, but with less intensity. Interestingly, all cpBVDV-1 activities were blocked by pharmacological inhibitors of the IRF-1, IRF-7, and NF-κB signaling pathway, and the level of IFNbeta decreased at the level of transcript and protein. These results, together with in silico analyses showing the presence of several regulatory consensus target motifs, suggest that cpBVDV-1 regulates IFNbeta expression in bovines through the activation of several key transcription factors. Collectively, the results suggest that during cpBVDV-1 infection, cross talk is evident between various signaling pathways involved in transcriptional activation of IFNbeta in cattle.