miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1

Carcinogenesis. 2014 Feb;35(2):469-78. doi: 10.1093/carcin/bgt330. Epub 2013 Oct 1.


Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that microRNAs (miRNAs) are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly downregulated in primary breast cancer, with greater downregulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased expression of miR-720 was correlated with lymph node metastasis. Furthermore, reexpression of miR-720 in breast cancer cells remarkably inhibited cell invasiveness and migration both in vitro and in vivo. Mechanistically, downregulation of TWIST1, a promoter of metastasis that was identified as a direct functional target of miR-720, was attributed to the inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast cancer, reexpression of miR-720 upregulated epithelial markers (E-cadherin and β-catenin) and downregulated mesenchymal markers (N-cadherin, fibronectin, vimentin and matrix metalloproteinase-2). Expression of miR-720 was inversely associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1 expression by small interfering RNA exhibited similar effects to reintroduction of miR-720, whereas overexpression of TWIST1 (without the 3'-untranslated region) abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate that miR-720 is frequently decreased in breast cancer and manifests antimetastatic activity by downregulating TWIST1, presenting a novel mechanism of miRNA-mediated regulation of tumor metastasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*


  • MIRN720 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Twist-Related Protein 1