Project description:Glioblastoma (GBM) in children is a relatively more common primary central nervous system tumor with a high degree of malignancy, high mortality, and complex surgical complete resection.. GNE987 is a newly developed von Hippel-Lindau tumor suppressor (VHL)-based pan-BET-targeting PROTAC, which can bind to the target proteins (BET proteins, including BRD2, BRD3, and BRD4) and recruit them to the ubiquitin/ proteasome system for degradation. However, the function of GNE987 has not been assessed in GBM cells so far. In the present study, ChIP-Seq analysis was performed to explore the effect of GNE987 on GBM cells.
Project description:To investigate the function of GNE987 in the regulation of gene expression, we treated U87 cells with control (DMSO) or GNE987, respectively. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and GNE987 treatment.
Project description:GNE987 is a newly developed von Hippel-Lindau tumor suppressor (VHL)-based pan-BET-targeting PROTAC, which can bind to the target proteins (BET proteins, including BRD2, BRD3, and BRD4) and recruit them to the ubiquitin/proteasome system for selective degradation. In the our study, ChIP-Seq analysis was performed to explore the effect of GNE987 on osteosarcoma cells.
Project description:Neuroblastoma (NB) is the most common extracranial solid tumor of childhood, which is derived from primordial neural crest cells. GNE987 is a newly developed von Hippel-Lindau tumor suppressor (VHL)-based pan-BET-targeting PROTAC, which can bind to the target proteins (BET proteins, including BRD2, BRD3, and BRD4) and recruit them to the ubiquitin/ proteasome system for selective degradation. However, the function of GNE987 has not been assessed in NB models so far. In the present study, RNA-seq analysis was performed to explore the effect of GNE987 on NB cells.
Project description:Neuroblastoma (NB) is the most common extracranial solid tumor of childhood, which is derived from primordial neural crest cells. GNE987 is a newly developed von Hippel-Lindau tumor suppressor (VHL)-based pan-BET-targeting PROTAC, which can bind to the target proteins (BET proteins, including BRD2, BRD3, and BRD4) and recruit them to the ubiquitin/ proteasome system for selective degradation. However, the function of GNE987 has not been assessed in NB models so far. In the present study, ChIP-Seq analysis was performed to explore the effect of GNE987 on NB cells.
Project description:PurposeAmong children, glioblastomas (GBMs) are a relatively common type of brain tumor. BRD4 expression was elevated in GBM and negatively correlated with the prognosis of glioma. We investigated the anti-GBM effects of a novel BRD4 inhibitor GNE987.MethodsWe evaluated the anti-tumor effect of GNE987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, the size of xenografts, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism.ResultsIn vitro experiments showed that GNE987 significantly degraded BRD4, inhibited the proliferation of GBM cells, blocked the cell cycle, and induced apoptosis. Similarly, in vivo experiments, GNE987 also inhibited GBM growth as seen from the size of xenografts and Ki67 immunohistochemical staining. Based on Western blotting, GNE987 can significantly reduce the protein level of C-Myc; meanwhile, we combined ChIP-seq with RNA-seq techniques to confirm that GNE987 downregulated the transcription of S100A16 by disturbing H3K27Ac. Furthermore, we validated that S100A16 is indispensable in GBM growth.ConclusionGNE987 may be effective against GBM that targets C-Myc expression and influences S100A16 transcription through downregulation of BRD4.