MiR-630 suppresses breast cancer progression by targeting metadherin

Oncotarget. 2016 Jan 12;7(2):1288-99. doi: 10.18632/oncotarget.6339.

Abstract

MicroRNAs have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-630 was reported to be deregulated and involved in tumor progression of several human malignancies. However, its expression regulation shows diversity in different kinds of cancers and its potential roles remain greatly elusive. Herein, we demonstrate that miR-630 is significantly suppressed in human breast cancer specimens, as well as in various breast cancer cell lines. In aggressive MDA-MB-231-luc and BT549 breast cancer cells, ectopic expression of miR-630 strongly inhibits cell motility and invasive capacity in vitro. Moreover, lentivirus delivered miR-630 bestows MDA-MB-231-luc cells with the ability to suppress cell colony formation in vitro and pulmonary metastasis in vivo. Further studies identify metadherin (MTDH) as a direct target gene of miR-630. Functional studies shows that MTDH contributes to miR-630-endowed effects including cell migration and invasion as well as colony formation in vitro. Taken together, these findings highlight an important role for miR-630 in the regulation of metastatic potential of breast cancer and suggest a potential application of miR-630 in breast cancer treatment.

Keywords: MTDH; breast cancer; metastasis; miR-630.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Membrane Proteins
  • Mice, Inbred NOD
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous

Substances

  • Cell Adhesion Molecules
  • MIRN630 microRNA, human
  • MTDH protein, human
  • Membrane Proteins
  • MicroRNAs
  • RNA-Binding Proteins