miR-20b is up-regulated in brain metastases from primary breast cancers

Oncotarget. 2015 May 20;6(14):12188-95. doi: 10.18632/oncotarget.3664.

Abstract

Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

Keywords: brain metastasis; breast cancer; miR-20b.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Metastasis
  • Prognosis
  • Risk Factors
  • Transfection
  • Up-Regulation

Substances

  • MicroRNAs