miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer

Br J Cancer. 2010 Mar 2;102(5):883-91. doi: 10.1038/sj.bjc.6605570. Epub 2010 Feb 16.


Background: We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145, which is the most down-regulated microRNA in BC.

Methods: We focused on fascin homologue 1 (FSCN1) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145.

Results: The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145, miR-133a, and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC (n=46) was significantly higher than in non-invasive BC (n=20) (P=0.0055).

Conclusion: Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carrier Proteins / genetics*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Luciferases / metabolism
  • Male
  • MicroRNAs / physiology*
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Transfection
  • Tumor Suppressor Proteins / physiology*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / prevention & control


  • Carrier Proteins
  • FSCN1 protein, human
  • MIRN133 microRNA, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Luciferases