ALKBH8 promotes bladder cancer growth and progression through regulating the expression of survivin

Biochem Biophys Res Commun. 2016 Aug 26;477(3):413-8. doi: 10.1016/j.bbrc.2016.06.084. Epub 2016 Jun 18.

Abstract

Human AlkB homolog 8 (ALKBH8) is highly expressed in high-grade, superficially and deeply invasive bladder cancer. Moreover, ALKBH8 knockdown induces apoptosis in bladder cancer cells. However, the underlying anti-apoptotic mechanism of ALKBH8 in bladder cancer cells has thus far remained unclear. Moreover, there is no direct evidence that highly expressed ALKBH8 is involved in tumor progression in vivo. We here show that ALKBH8 knockdown induced apoptosis via downregulating the protein expression of survivin, an anti-apoptotic factor also exhibiting increased levels in bladder cancer. We also clarify that ALKBH8 transgenic mice showed an accelerated rate of bladder tumor mass and invasiveness in an N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced bladder cancer model. These findings suggest that the high expression of ALKBH8 is critical for the growth and progression of bladder cancer.

Keywords: ALKBH8; Anti-apoptotic factor; Bladder cancer; Tumor progression.

MeSH terms

  • AlkB Homolog 8, tRNA Methyltransferase / genetics
  • AlkB Homolog 8, tRNA Methyltransferase / physiology*
  • Animals
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Survivin
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Survivin
  • ALKBH8 protein, human
  • AlkB Homolog 8, tRNA Methyltransferase