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Background:Glioblastoma is the most common form of malignant brain cancer and has a poor prognosis in adults. We identified Dhx15 as a candidate tumour suppressor gene in glioma by transposon-based mutagenesis. Dhx15 is an adenosine triphosphate (ATP)-dependent RNA helicase belonging to the DEAH-box (DHX) helicase family, but its role in cancer remains elusive.Methods:DHX15 expression levels were examined in glioma cell lines. DHX15 functions were examined by gain- and loss-of-function analyses. Protein motifs required for the function of DHX15 were investigated by the analysis of mutant proteins.Results:DHX15 expression was lower in human glioma cell lines than in normal neural stem cells. Dhx15 knockdown resulted in enhanced proliferation of primary immortalised mouse astrocytes, supporting the notion that DHX15 is a tumour suppressor. Retroviral-mediated transduction of DHX15 into glioma cell lines suppressed proliferation and foci formation in vitro. Moreover, DHX15 suppressed tumour formation in a xenograft mouse model. ATPase activity was not required for the growth-inhibitory function of DHX15; however, the Ia, Ib, IV, and V motifs, which act as RNA-binding domains in DHX15, were essential. qPCR analysis revealed that DHX15 suppressed expression of NF-κB downstream target genes as well as the genes involved in splicing.Conclusions:These findings provide evidence that DHX15 acts as a tumour suppressor gene in glioma. [ABSTRACT FROM AUTHOR]

To provide a more comprehensive understanding of the genes and evolutionary forces driving colorectal cancer (CRC) progression, we performed Sleeping Beauty (SB) transposon mutagenesis screens in mice carrying sensitizing mutations in genes that act at different stages of tumor progression. This approach allowed us to identify a set of genes that appear to be highly relevant for CRC and to provide a better understanding of the evolutionary forces and systems properties of CRC. We also identified six genes driving malignant tumor progression and a new human CRC tumor-suppressor gene, ZNF292, that might also function in other types of cancer. Our comprehensive CRC data set provides a resource with which to develop new therapies for treating CRC. [ABSTRACT FROM AUTHOR]