title: SWAP70, actin-binding protein, function as an oncogene targeting tumor-suppressive miR-145 in prostate cancer.
abstract: BACKGROUND
  MiR-145 is down-regulated in various human cancers. We previously demonstrated that some actin-binding proteins were targeted by several microRNAs (miRNAs), including miR-145, in bladder and prostate cancer (CaP). The aim of this study is to determine a novel oncogenic gene targeted by miR-145 by focusing on actin-binding proteins in CaP.
  
  
  METHODS
  We focused on the SWAP switching B-cell complex 70 kDa subunit (SWAP70), which is an F-actin binding protein involved in activating B-cell transformation. A luciferase reporter assay was used to identify the actual binding sites between miR-145 and SWAP70 mRNA. Cell viability was evaluated by cell proliferation, wound healing, and matrigel invasion assays in si-SWAP70 transfectants. A total of 75 clinical prostate specimens were subjected to immunohistochemistry of SWAP70.
  
  
  RESULTS
  Molecular target searches of this miRNA and the luciferase reporter assay showed that SWAP70 was directly regulated by miR-145. Silencing of SWAP70 studies demonstrated significant inhibitions of cell migration and invasion in CaP cell lines. The SWAP70 positive-staining was significantly higher in percentage in the CaP than in benign prostate hyperplasia tissue.
  
  
  CONCLUSIONS
  Down-regulation of miR-145 was a frequent event in CaP, and it may have a tumor suppressive function. SWAP70 may be a target of miR-145, and it might have a potential oncogenic function. The novel molecular networks though which miR-145 acts, may provide new insights into the underlying molecular mechanisms of CaP.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tatarano
authors.forename: Kazumori
authors.initials: K
authors.lastname: Kawakami
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Nijiro
authors.initials: N
authors.lastname: Nohata
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C491873:SWAP70 protein, human; D008156:Luciferases