title: The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer.
abstract: BACKGROUND
  On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs.
  
  
  RESULTS
  We investigated the miRNA expression signature of BC clinical specimens and identified several downregulated miRNAs (miR-133a, miR-204, miR-1, miR-139-5p, and miR-370). MiR-1 and miR-133a showed potential role of tumour suppressors by functional analyses of BC cells such as cell proliferation, apoptosis, migration, and invasion assays. Molecular target searches of these miRNAs showed that transgelin 2 (TAGLN2) was directly regulated by both miR-1 and miR-133a. Silencing of TAGLN2 study demonstrated significant inhibitions of cell proliferation and increase of apoptosis in BC cell lines. The immunohistochemistry showed a positive correlation between TAGLN2 expression and tumour grade in clinical BC specimens.
  
  
  CONCLUSIONS
  The downregulation of miR-1 and miR-133a was a frequent event in BC, and these miRNAs were recognised as tumour suppressive. TAGLN2 may be a target of both miRNAs and had a potential oncogenic function. Therefore, novel molecular networks provided by miRNAs may provide new insights into the underlying molecular mechanisms of BC.
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshino
authors.forename: T
authors.initials: T
authors.lastname: Chiyomaru
authors.forename: H
authors.initials: H
authors.lastname: Enokida
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.forename: S
authors.initials: S
authors.lastname: Tatarano
authors.forename: K
authors.initials: K
authors.lastname: Nishiyama
authors.forename: N
authors.initials: N
authors.lastname: Nohata
authors.forename: N
authors.initials: N
authors.lastname: Seki
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin