RNA helicase DHX15 acts as a tumour suppressor in glioma

Br J Cancer. 2017 Oct 24;117(9):1349-1359. doi: 10.1038/bjc.2017.273. Epub 2017 Aug 22.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Female
  • Genes, Tumor Suppressor*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, Nude
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • DHX15 protein, human
  • RNA Helicases