4.4 Article

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

Journal

PROSTATE
Volume 73, Issue 10, Pages 1082-1089

Publisher

WILEY-BLACKWELL
DOI: 10.1002/pros.22656

Keywords

miR-152; TGF alpha; molecular target

Funding

  1. Program for Development of Innovative Research Team in the First Affiliated Hospital of Nanjing Medical University
  2. Provincial Initiative Program for Excellency Disciplines of Jiangsu Province
  3. National Natural Science Foundation of China [81171963, 81102089, 81201998]
  4. Natural Science Foundation of Jiangsu Province [BK2011773]

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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 (TGF) 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 TGF 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 TGF 3-UTR. RESULTS TGF 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 TGF knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro. TGF is a direct target gene of miR-152. CONCLUSIONS Our findings suggest that miR-152 can act as a tumor suppressor that targets TGF. miR-152 is a promising molecular target that inhibits PCa cell migration and invasion. Prostate 73: 1082-1089, 2013. (c) 2013 Wiley Periodicals, Inc.

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