Project description:Overexpression of histone deacetylases (HDACs) in cancer commonly causes resistance to genotoxic based therapies. Here we report on the novel mechanism whereby overexpressed class I HDACs increase the resistance of glioblastoma cells to the SN1 methylating agent temozolomide (TMZ). The chemotherapeutic TMZ triggers the activation of the DNA damage response (DDR) in resistant glioma cells, leading to DNA lesion bypass and cellular survival. Mass spectrometry analysis revealed that the catalytic activity of class I HDACs stimulates the expression of the E3 ubiquitin ligase RAD18. Furthermore, the data show that RAD18 is part of the O6-methylguanine-induced DDR as TMZ induces the formation of RAD18 foci at sites of DNA damage. Downregulation of RAD18 by HDAC inhibition prevents glioma cells from activating the DDR upon TMZ exposure. Lastly, RAD18 or O6-methylguanine-DNA methyltransferase (MGMT) overexpression abolishes the sensitization effect of HDAC inhibition on TMZ-exposed glioma cells. Our study describes the mechanism whereby class I HDAC overexpression in glioma cells causes resistance to TMZ treatment. HDACs accomplish this by promoting the bypass of O6-methylguanine DNA lesions via enhancing RAD18 expression. It also provides a treatment option with HDAC inhibition to undermine this mechanism.
Project description:As a member of the polycomb group, PCGF1 play a vital role in the development of embryo nervus system. But our recent studies suggested PCGF1 may involved in the development, progression and relapse of glioma. We used microarrays to detail the different expression of gene following the knockdown of PCGF1 expression in U87 cells.
Project description:This SuperSeries is composed of the following subset Series: GSE34454: Expression data from transfection of SW1783 glioma cells with microRNA-376a* for 24 hours GSE34455: Expression data from transfection of U87 glioma cells with miR-376a* for 24 hours GSE34456: Expression data from transfection of U87 glioma cells with miR-376a* for 72 hours Refer to individual Series
Project description:Glioma cells are sensitized to the alkylator temozolomide after exposure to IFN-beta. In glioma-initiating cells (GIC), IFN-beta alone reduces clonogenicity. We investigated differentially expressed genes with or without IFN exposure in either longterm glioma cells or GIC. We used microarrays to investigate differential gene regulation in glioma cells after exposure to either ddH20 or IFN-beta 300 IU/ml at 6 h or 24 h.
