miR-340 inhibition of breast cancer cell migration and invasion through targeting of oncoprotein c-Met

Cancer. 2011 Jul 1;117(13):2842-52. doi: 10.1002/cncr.25860. Epub 2011 Jan 10.

Abstract

Background: Different microRNAs have been shown to have oncogenic and tumor-suppressive functions in human cancers. Detection of their expression may lead to identifying novel markers for breast cancer.

Methods: The authors detected miR-340 expression in 4 human breast cell lines and then focused on its role in regulation of tumor cell growth, migration, and invasion and target gene expression. They then analyzed miR-340 expression in benign and cancerous breast tissue specimens.

Results: Endogenous miR-340 expression was down-regulated in the more aggressive breast cancer cell lines, which was confirmed in breast cancer tissue specimens by using quantitative real-time polymerase chain reaction. Further studies showed that induction of miR-340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR-340 expression induced breast cancer cell migration and invasion. At the gene level, the authors identified c-Met as a direct miR-340 target to mediate cell migration and invasion through regulation of MMP-2 and MMP-9 expression. Ex vivo, loss of miR-340 expression was associated with lymph node metastasis, high tumor histological grade, clinical stage, and shorter overall survival of breast cancer as well as increased c-Met expression in breast cancer tissue specimens.

Conclusions: miR-340 may play an important role in breast cancer progression, suggesting that miR-340 should be further evaluated as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization
  • Lymphatic Metastasis / genetics
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Neoplasm Invasiveness*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • RNA, Small Interfering
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism*
  • Survival Rate

Substances

  • RNA, Small Interfering
  • Receptors, Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9