MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin

Oncogene. 2014 Jun 12;33(24):3119-28. doi: 10.1038/onc.2013.286. Epub 2013 Jul 15.

Abstract

Accumulating data have shown the involvement of microRNAs in cancerous processes as either oncogenes or tumor suppressor genes. Here, we established miR-30a as a tumor suppressor gene in breast cancer development and metastasis. Ectopic expression of miR-30a in breast cancer cell lines resulted in the suppression of cell growth and metastasis in vitro. Consistently, the xenograft mouse model also unveiled the suppressive effects of miR-30a on tumor growth and distal pulmonary metastasis. With dual luciferase reporter assay, we revealed that miR-30a could bind to the 3'-untranslated region of metadherin (MTDH) gene, thus exerting inhibitory effect on MTDH. Furthermore, we demonstrated that silence of MTDH could recapitulate the effects of miR-30a overexpression, while overexpression of MTDH could partially abrogate miR-30a-mediated suppression. Of significance, expression level of miR-30a was found to be significantly lower in primary breast cancer tissues than in the paired normal tissues. Further evaluation verified that miR-30a was negatively correlated with the extent of lymph node and lung metastasis in patients with breast cancer. Taken together, our findings indicated miR-30a inhibits breast cancer proliferation and metastasis by directly targeting MTDH, and miR-30a can serve as a prognostic marker for breast cancer. Manipulation of miR-30a may provide a promising therapeutic strategy for breast cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / prevention & control
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / prevention & control
  • Carcinoma, Lobular / secondary
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Cell Adhesion Molecules / genetics
  • Cell Movement*
  • Cell Proliferation*
  • DNA Primers / chemistry
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Luciferases / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • Cell Adhesion Molecules
  • DNA Primers
  • MIRN30b microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • Luciferases