miR-152 controls migration and invasive potential by targeting TGFα in prostate cancer cell lines

Prostate. 2013 Jul;73(10):1082-9. doi: 10.1002/pros.22656. Epub 2013 Mar 4.

Abstract

Background: MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in diverse biological processes. Aberrant miR-152 expression has been frequently reported in various malignant tumors. However, the mechanism of miR-152 in prostate cancer (PCa) remains unclear. This study aims to determine the function of miR-152 in PCa cells and identify the novel molecular targets regulated by miR-152.

Methods: The expression levels of transforming growth factor-alpha (TGFα) were determined in three samples of PCa and adjacent non-tumorous tissues by Western blot analysis. miR-152 levels in 48 primary PCa and 15 non-malignant tissue samples were measured by qRT-PCR. The effects of forced miR-152 expression or TGFα knockdown on PCa cells were evaluated by cell migration and invasion assays, as well as Western blot analysis. Dual-luciferase reporter assay was used to identify binding sites between miR-152 and TGFα 3'-UTR.

Results: TGFα was upregulated in PCa tissue samples compared with that in adjacent normal ones. miR-152 expression was significantly decreased in primary PCa samples compared with that in non-malignant samples. Patients with Gleason scores >7 exhibited lower miR-152 levels than those with lower scores. Moreover, low miR-152 expression is correlated with advanced pathological T-stages. Forced miR-152 expression or TGFα knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGFα is a direct target gene of miR-152.

Conclusions: Our findings suggest that miR-152 can act as a tumor suppressor that targets TGFα. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Transforming Growth Factor alpha / genetics
  • Transforming Growth Factor alpha / metabolism*
  • Up-Regulation / genetics

Substances

  • MIRN152 microRNA, human
  • MicroRNAs
  • Transforming Growth Factor alpha