miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc

Oncol Rep. 2016 Oct;36(4):2049-58. doi: 10.3892/or.2016.5040. Epub 2016 Aug 25.


MicroRNA (miRNA) expression is shown dysregulated in tumors. It has been reported that miR-451 alters gene expression and regulates tumorigenesis in various cancer tissues. However, its underlying biological significance in bladder cancer remains to be clarified. In the present study, we investigated the function and molecular mechanism of miR-451 involved in bladder cancer cell migration and invasion. Our results showed that miR-451 was downregulated in clinical bladder carcinoma tissues compared with adjacent bladder tissues. Overexpression of miR-451 significantly retarded the proliferation, migration and invasion of bladder cancer T24 and 5637 cells in vitro. Moreover, the attenuated cell migration and invasion by miR-451 was correlated with increased apoptosis. However, our dual-luciferase reporter assay validated that c-Myc, an oncogene in many tumors, was a direct target gene of miR-451 in bladder cancer. The expression of c-Myc was repressed by miR-451 in bladder cancer cells, and knockdown of c-Myc mimicked the effects of miR-451 overexpression. This discovery suggested that miR-451 is a tumor suppressor modulating bladder cancer cell migration and invasion by directly targeting c-Myc. In addition, apoptosis promoted by miR-451 may participates in this biological behavior. Therefore, target miR-451 may be a novel therapeutic intervention for bladder cancer.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology*
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*


  • MIRN451 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc