MicroRNA-10b targets E-cadherin and modulates breast cancer metastasis

Med Sci Monit. 2012 Aug;18(8):BR299-308. doi: 10.12659/msm.883262.

Abstract

Background: Recent studies have suggested that microRNA-10b (miR-10b) acts as a promoter of metastasis in breast cancer, although the underlying mechanism remains largely unknown. In this study, we provide the first evidence that E-cadherin (E-cad) is a potential target of miR-10b.

Material/method: By applying gain-of-function and loss-of-function approaches in the metastatic breast cancer cell line MDA-MB-231, we demonstrated that miR-10b is necessary and sufficient to regulate the cellular expression of E-cad and in vitro tumor cell invasion.

Results: Comparative expression analysis of miR-10b in benign breast lesions (N=16), primary breast cancers (N=21), and metastatic breast carcinomas (N=23) revealed that miR-10b transcription was uniquely up-regulated in metastatic cancers. The expression level of miR-10b positively correlated with tumor size, pathological grading, clinical staging, lymph node metastasis, Her2-positivity and tumor proliferation, but was negatively associated with estrogen receptor-positivity, progesterone receptor-positivity and E-cad mRNA and protein levels.

Conclusions: These findings indicate the existence of a novel E-cadherin-related mechanism by which miR-10b modulates breast cancer metastasis. In addition, miR-10b may be a useful biomarker of advanced progression and metastasis of breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Linear Models
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Molecular Sequence Data
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Up-Regulation / genetics

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIRN10 microRNA, human
  • MicroRNAs