miR205 inhibits stem cell renewal in SUM159PT breast cancer cells

PLoS One. 2017 Nov 28;12(11):e0188637. doi: 10.1371/journal.pone.0188637. eCollection 2017.

Abstract

miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed the impact of miR205 ectopic expression in the initial tumorigenic processes of SUM159PT, a triple negative breast cancer cell line with low endogenous levels of miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3, Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels, while increased p27kip1 expression. miR205 abolished anchorage-independent growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and levels of secreted MMP9. miR205 also reduced expression of CD44 and TAZ, E2A.E12, Twist, Snail1 and CK5, associated with epithelial-mesenchymal transition (EMT). Importantly, we show that miR205 inhibited SUM159PT cancer-stem cell renewal, expression in mammospheres of CD44 and ALDH1 stem-cell markers, TAZ, and E2A.E12. All these effects of miR205 were reverted by Anti-miR205 co-expression, demonstrating its specificity. Thus, all these results strongly suggest that ectopic expression of miR205 in SUM159PT affected several parameters associated with initial steps of tumorigenesis.

MeSH terms

  • Breast Neoplasms / pathology*
  • Humans
  • MicroRNAs / physiology*
  • Neoplastic Stem Cells / pathology*

Substances

  • MIRN205 microRNA, human
  • MicroRNAs

Grant support

These studies have been supported by grants from Ministerio de Economia y Competitividad from Spain (SAF2012-38048 and SAF2016-75991-R) to J. M-P, as well as a fellowship to María Pilar Sánchez-Bailón.