miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway

J Cell Mol Med. 2019 Sep;23(9):6295-6307. doi: 10.1111/jcmm.14515. Epub 2019 Jul 5.


miR-516a-3p has been reported to play a suppressive role in several types of human tumours. However, the expression level, biological function and fundamental mechanisms of miR-516a-3p in breast cancer remain unclear. In the present study, we found that miR-516a-3p expression was down-regulated and Pygopus2 (Pygo2) expression was up-regulated in human breast cancer tissues and cells. Through analysing the clinicopathological characteristics, we demonstrated that low miR-516a-3p expression or positive Pygo2 expression was a predictor of poor prognosis for patients with breast cancer. The results of a dual luciferase reporter assay and Western blot analysis indicated that Pygo2 was a target gene of miR-516a-3p. Moreover, overexpression of miR-516a-3p inhibited cell growth, migration and invasion as well as epithelial-mesenchymal transition (EMT) of breast cancer cells, whereas reduced miR-516a-3p expression promoted breast cancer cell growth, migration, invasion and EMT. Furthermore, we showed that miR-516a-3p suppressed cell proliferation, metastasis and EMT of breast cancer cells by inhibiting Pygo2 expression. We confirmed that miR-516a-3p exerted an anti-tumour effect by inhibiting the activation of the Wnt/β-catenin pathway. Finally, xenograft tumour models were used to show that miR-516a-3p inhibited breast cancer cell growth and EMT via suppressing the Pygo2/Wnt signalling pathway. Taken together, these results show that miR-516a-3p inhibits breast cancer cell growth, metastasis and EMT by blocking the Pygo2/ Wnt/β-catenin pathway.

Keywords: Pygo2; Wnt; breast cancer; epithelial-mesenchymal transition; miR-516a-3p.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MicroRNAs / genetics*
  • Middle Aged
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics


  • Intracellular Signaling Peptides and Proteins
  • MIRN516 microRNA, human
  • MicroRNAs
  • PYGO2 protein, human
  • beta Catenin