MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/β-catenin signaling in breast cancer

Oncotarget. 2016 Apr 26;7(17):24076-87. doi: 10.18632/oncotarget.8119.


Constitutive activation of the Wnt/β-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and β-catenin, contribute to aberrant activation of the Wnt/β-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/β-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/β-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/β-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3β (GSK-3β), and inhibitor of β-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer.

Keywords: Wnt/β-catenin pathway; breast cancer; miR-1229; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Prognosis
  • Tumor Cells, Cultured
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Biomarkers, Tumor
  • MicroRNAs
  • Wnt Proteins
  • beta Catenin