MiR-339-5p inhibits breast cancer cell migration and invasion in vitro and may be a potential biomarker for breast cancer prognosis

BMC Cancer. 2010 Oct 9:10:542. doi: 10.1186/1471-2407-10-542.

Abstract

Background: MicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Detection of their expression may lead to identifying novel markers for breast cancer.

Methods: We profiled miRNA expression in three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and then focused on one miRNA, miR-339-5p, for its role in regulation of tumor cell growth, migration, and invasion and target gene expression. We then analyzed miR-339-5p expression in benign and cancerous breast tissue specimens.

Results: A number of miRNAs were differentially expressed in these cancer cell lines. Real-time PCR indicated that miR-339-5p expression was downregulated in the aggressive cell lines MDA-MB-468 and MDA-MB-231 and in breast cancer tissues compared with benign tissues. Transfection of miR-339-5p oligonucleotides reduced cancer cell growth only slightly but significantly decreased tumor cell migration and invasion capacity compared with controls. Real-time PCR analysis showed that BCL-6, a potential target gene of miR-339-5p, was downregulated in MDA-MB-231 cells by miR-339-5p transfection. Furthermore, the reduced miR-339-5p expression was associated with an increase in metastasis to lymph nodes and with high clinical stages. Kaplan-Meier analyses found that the patients with miR-339-5p expression had better overall and relapse-free survivals compared with those without miR-339-5p expression. Cox proportional hazards analyses showed that miR-339-5p expression was an independent prognostic factor for breast cancer patients.

Conclusions: MiR-339-5p may play an important role in breast cancer progression, suggesting that miR-339-5p should be further evaluated as a biomarker for predicting the survival of breast cancer patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor
  • Breast / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Female
  • Humans
  • In Situ Hybridization
  • In Vitro Techniques
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-6
  • Wound Healing

Substances

  • BCL6 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • MIRN339 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6