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

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. M...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2016-08, Vol.477 (3), p.413-418
Main Authors: Ohshio, Ikumi, Kawakami, Ryoji, Tsukada, Yohei, Nakajima, Kazuhiro, Kitae, Kaori, Shimanoe, Tomoki, Saigo, Yasuka, Hase, Hiroaki, Ueda, Yuko, Jingushi, Kentaro, Tsujikawa, Kazutake
Format: Article
Language:English
Subjects:
AlkB Homolog 8, tRNA Methyltransferase - genetics
AlkB Homolog 8, tRNA Methyltransferase - physiology
ALKBH8
Animals
Anti-apoptotic factor
Apoptosis - physiology
Bladder cancer
Cell Line, Tumor
Disease Progression
Humans
Inhibitor of Apoptosis Proteins - metabolism
Mice
Mice, Transgenic
Tumor progression
Urinary Bladder Neoplasms - metabolism
Urinary Bladder Neoplasms - pathology
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Summary: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. •ALKBH8 induced survivin to regulate apoptosis in bladder cancer cells.•ALKBH8 transgenic mice showed marked tumor progression in a bladder cancer model.•ALKBH8 transgenic mice showed increased invasiveness of BBN-induced bladder cancer.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2016.06.084