miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1

Breast Cancer Res Treat. 2011 Apr;126(3):565-75. doi: 10.1007/s10549-010-0954-4. Epub 2010 May 27.

Abstract

MicroRNAs have been implicated in regulating diverse cellular pathways. Emerging evidence indicate that the miR-17-92 cluster may have a causal role in breast cancer tumorigenesis as a novel class of oncogenes, but the role of these miRNAs in breast cancer invasion and migration remains unexplored. The aims of this study were to verify the effect of miR-17-5p (an important member of the miR-17-92 cluster) on the invasive and migratory ability of breast cancer cells. The matching of miR-17-5p and HMG box-containing protein 1 (HBP1) was predicted by TargetScan and confirmed by DNA constructs and luciferase target assay. The expression levels of miR-17-5p and its candidate target-HBP1 in MCF7 and MDA-MB-231 breast cancer cells were measured by real-time PCR and western blotting. Effects of miR-17-5p in cell cycle progression, proliferation, invasion and migration were evaluated by flow cytometry assay, 3-(4,-dimethy -lthiazol-2-yl)-2,-diphenyl -tetrazoliumbromide assay, soft-agar colony formation assay, and transwell invasive and migratory assay, respectively. The results showed that miR-17-5p was highly expressed in high-invasive MDA-MB-231 breast cancer cells but not in low-invasive MCF-7 breast cancer cells. Over-expression of miR-17-5p in MCF-7 cells rendered them the invasive and migratory abilities by targeting HBP1/β-catenin pathway. On the other hand, down-regulation of endogenous miR-17-5p suppressed the migration and invasion of MDA-MB-231 cells in vitro. These findings suggest that miR-17-5p plays an important role in breast cancer cell invasion and migration by suppressing HBP1 and subsequent activation of Wnt/β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Flow Cytometry / methods
  • Gene Expression Regulation, Neoplastic*
  • High Mobility Group Proteins / biosynthesis
  • High Mobility Group Proteins / physiology*
  • Humans
  • MicroRNAs / biosynthesis*
  • Neoplasm Invasiveness
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • HBP1 protein, human
  • High Mobility Group Proteins
  • MIRN17 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Tetrazolium Salts
  • Thiazoles
  • Wnt Proteins
  • beta Catenin
  • thiazolyl blue