title: Silencing of ATPase Inhibitory Factor 1 Inhibits Cell Growth via Cell Cycle Arrest in Bladder Cancer.
abstract: OBJECTIVE
  The role of the ATPase inhibitory factor 1 (IF1) is inhibit the hydrolase activity of F1Fo-ATPase when oxidative phosphorylation is impaired. It has been demonstrated that IF1 is overexpressed in various carcinomas and mediates tumor cell activities, but the detailed mechanisms of IF1-mediated tumor progression and the link between IF1 and cell cycle progression remain unclear. Herein, we aimed to investigate the potential role of IF1 in cell cycle progression of human bladder cancer (BCa).
  
  
  METHODS
  The expression of IF1 was analyzed by immunohistochemistry in tumor tissues. Western blot was used to detect protein expression in the cells. Cell proliferation was determined by MTT and colony formation assays. The cell cycle was analyzed using flow cytometry.
  
  
  RESULTS
  We firstly showed IF1 was overexpressed in BCa. Silencing of IF1 by small interfering RNA led to a significant decrease in cell proliferation and migration in T24 and UM-UC-3 cells. Importantly, IF1 knockdown caused cell cycle arrest at G0/G1 stage and decreased the protein level of cyclin E/cyclin-dependent kinases (cdk) 2 and/or cyclin D/cdk4/cdk6.
  
  
  CONCLUSIONS
  These results suggest the inhibitory effect of IF1 knockdown on BCa cell proliferation is via the suppression of cyclins and cdks related to G1/S transition and then induction of G0/G1 arrest, and firstly indicate IF1 mediates the tumor cell cycle. We concluded that IF1 may be a novel therapeutic target for BCa.
authors.affiliation: Department of Urology, Kochi Medical School, Nankoku, Kochi, Japan.
authors.forename: Shihu
authors.initials: S
authors.lastname: Wei
authors.forename: Hideo
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurabayashi
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furihata
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Ogura
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D000097795:ATPase Inhibitory Protein
chemical_list: D051357:Cyclin-Dependent Kinase 2; D051361:Cyclin-Dependent Kinase 6; D016213:Cyclins; D011506:Proteins; D034741:RNA, Small Interfering; D000097795:ATPase Inhibitory Protein; C495894:CDK2 protein, human; C495911:CDK6 protein, human