title: ALKBH8 promotes bladder cancer growth and progression through regulating the expression of survivin.
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.
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Ohshio
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kawakami
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tsukada
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kitae
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Shimanoe
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yasuka
authors.initials: Y
authors.lastname: Saigo
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hase
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: jingushi-kk@phs.osaka-u.ac.jp.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Jingushi
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
mesh_terms: D000071503:AlkB Homolog 8, tRNA Methyltransferase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C549623:ALKBH8 protein, human; D000071503:AlkB Homolog 8, tRNA Methyltransferase
keywords: ALKBH8; Anti-apoptotic factor; Bladder cancer; Tumor progression