Project description:PUS7, a pseudouridine synthase, plays a critical role in growth, self-renewal, and tumorigenesis of glioblastoma stem cells. We used RNA-seq to investigate the global gene expression regulated by PUS7 and identified downstream pathway of PUS7 in glioblastoma stem cells.
Project description:Pseudouridine is the first discovered and the most frequent modification in RNA. However, its biological functions in physiology and human diseases are largely unknown. Here, we show that pseudouridine synthase PUS7 is differentially expressed in glioblastoma patient tissues verse non-tumor brain tissues, and highly expressed in patient brain-derived cancer stem cells, compared to normal brain-derived neural stem cells. Upregulated expression of PUS7 predicts worse survival in glioblastoma patients in multiple databases. Indeed, we show that PUS7 plays an important role in regulating the self-renewal and tumorigenesis of glioblastoma stem cells. Overexpression of the wild type but not the catalytically inactive PUS7 increases the growth and self-renewal of GSCs. In contrast, knockdown of PUS7 dramatically suppresses GSC growth, self-renewal and tumorigenesis. Mechanistically, knockdown of PUS7 activates interferon pathway through translational control of TYK2 via PUS7-regulated tRNAs. Moreover, we have identified chemical inhibitors for PUS7 in this study. These chemical compounds target pseudouridine modification and suppress GSC growth and tumorigenesis, providing a potential therapeutic tool for GBM treatment.
Project description:TLX (NR2E1), as an orphan nuclear receptor, plays a critical role in growth, self-renewal, and tumorigenesis of glioblastoma stem cells. We used microarrays to investigate the global gene expression regulated by TLX and identified downstream targets of TLX in glioblastoma stem cells. We further investigated the global gene expression regulated by TET3, a downstream target of TLX, to identified downstream targets of TLX-TET3 axis in glioblastoma stem cells.