title: Regulation of E3 ubiquitin ligase-1 (WWP1) by microRNA-452 inhibits cancer cell migration and invasion in prostate cancer.
abstract: MicroRNA-224 (miR-224) and microRNA-452 (miR-452) are closely located on the human chromosome Xq28 region. miR-224 functions as a tumour suppressor by targeting tumour protein D52 (TPD52) in prostate cancer (PCa). Here, we aimed to investigate the functional significance of miR-452 in PCa cells.
  
  
  
  Functional studies of PCa cells were performed using transfection with mature miRNAs or siRNAs. Genome-wide gene expression analysis, in silico analysis, and dual-luciferase reporter assays were applied to identify miRNA targets. The association between miR-452 levels and overall patient survival was estimated by the Kaplan-Meier method.
  
  
  
  Expression of miR-452 was significantly downregulated in PCa tissues. Transfection with mature miR-452 inhibited the migration and invasion of PCa cells. Kaplan-Meier survival curves showed that low expression of miR-452 predicted a short duration of progression to castration-resistant PCa. WW domain-containing E3 ubiquitin protein ligase-1 (WWP1) was a direct target of miR-452, and knockdown of WWP1 inhibited the migration and invasion of PCa cells. WWP1 was upregulated in PCa clinical specimens.
  
  
  
  Regulation of the miR-452-WWP1 axis contributed to PCa cell migration and invasion, and elucidation of downstream signalling of this axis will provide new insights into the mechanisms of PCa oncogenesis and metastasis.
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Urology, Teikyo University Chiba Medical Centre, Chiba 299-0111, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kurozumi
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okato
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: C574051:MIRN452 microRNA, human; D035683:MicroRNAs; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases