Project description:The transcriptional repressor ZBTB18 was overexpressed in the brain tumor stem cell-like BTSC233 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.
Project description:The transcriptional repressor ZBTB18 was overexpressed in the brain tumor xenoline JX6 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.
Project description:ZBTB18 is a transcriptional repressor and tumor suppressor in glioblastoma (GBM). Specifically, it acts as a repressor of mesenchymal genes. ZBTB18 interacts with C-terminal binding proteins 1 and 2 through a VLDL motif. In GBM, ZBTB18 is cleaved the the calpain 2 intracellular proteases which generates truncated Nte and Cte short forms. Here we have investigated gene expression changes which occur upon the expression of ZBTB18 full lenght or ZBTB18 short form Nte (SF-Nte), as well as upon expression of the mutated counterparts which no longer interacts with CTBP1/2.
Project description:Background. Glioma associated macrophages/microglia (GAMs) are massively recruited to the tumor site where they commit to a tumor promoting phenotype, driving glioblastoma progression. GAMs secrete several factors that facilitate tumor proliferation and invasion, and prevent an effective immune response against glioblastoma. Here, we investigate how the tumor suppressor ZBTB18 affects GAMs and ultimately shapes the tumor microenvironment. Methods. The regulation of cytokine expression and secretion was assessed by gene expression and cytokine arrays. The effect of ZBTB18 expression on microglia properties was investigated in vivo in mouse xenografts and by RNAseq of microglia cells conditioned with the medium of ZBTB18-expressing patient-derived GBM cells. The analysis was further extended to TAM scRNAseq data (GBMap). Results. Here, we demonstrate that ZBTB18, a transcriptional repressor with tumor suppressive function in glioblastoma, impairs the production of key chemokines responsible for GAM recruitment. Consistently, we observe a reduced migration of GAMs towards ZBTB18-expressing glioblastoma cells, both in cell culture and in vivo experiments. Moreover, RNA sequencing analysis shows that the presence of ZBTB18 in glioblastoma cells alters the commitment of conditioned microglia, suggesting the loss of the immunosuppressive phenotype. Conclusions. Our data indicate that, by blocking the release of key cytokines, ZBTB18 modifies microglia behavior, counteracting their tumor-promoting function. Thus, therapeutic approaches to increase ZBTB18 expression in glioblastoma cells could represent an effective adjuvant to immunotherapy in the treatment of this kind of tumor.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6
