Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation

Cancer Biol Ther. 2014 Oct;15(10):1404-12. doi: 10.4161/cbt.29923. Epub 2014 Jul 21.


In breast cancer cells, heterodimerization of HER2 and HER3 plays important and dominant roles in the functionality and transformation of HER-mediated pathways, in particular the PI3K/Akt survival pathway. HER3 was considered as a major signaling hub in HER2-amplified cancers. Inhibition of HER3 expression may therefore represent a rational therapeutic approach to breast cancers where HER2/HER3-mediated signaling plays a role in tumorigenesis and progression. miRNAs exerts important roles in regulating gene expressions by binding to and repressing target mRNAs. Here we reported that miRNA-450b-3p inhibits HER3 expression by directly targeting 3' UTR of HER3 mRNA and represses the downstream signal transductions of HER family. Overexpression of miRNA-450b-3p in SKBR3 cells inhibits cells clonogenic potential and enhances their sensitivity to trastuzumab, a monoclonal antibody that binds to the HER2 receptor, or doxorubicin through repressing proliferative signal pathways mediated by HER3/HER2/PI3K/AKT. Furthermore, we found that breast cancer patients with tumors that demonstrating upregulated HER3 (> 2-fold) and downregulated miR-450b-3p (> 2-fold) expressions compared with the paired adjacent non-tumorous tissues showed significantly poorer overall survival (P<0.05). Our study identified miRNA-450b-3p as a new tumor repressor and also provided some evidences suggesting that downregulation of miR-450b-3p expression with concurrent overexpression of HER3 may serve as a prognostic biomarker for poor overall survival in breast cancer patients.

Keywords: HER3; breast cancer; miRNA-450b-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Doxorubicin / pharmacology
  • Female
  • Heterografts
  • Humans
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-3 / metabolism*
  • Trastuzumab


  • 3' Untranslated Regions
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • MIRN450 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Doxorubicin
  • Phosphatidylinositol 3-Kinases
  • Receptor, ErbB-3
  • Oncogene Protein v-akt
  • Trastuzumab