MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells

BMC Genomics. 2013 Feb 28;14:139. doi: 10.1186/1471-2164-14-139.

Abstract

Background: A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells (BT-ICs) may open the road for novel therapeutic strategies. As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions.

Results: We found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression.

Conclusions: miR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic
  • Female
  • Gene Expression Profiling*
  • MCF-7 Cells
  • Membrane Proteins / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Reproducibility of Results

Substances

  • AVEN protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • MIRN30b microRNA, human
  • Membrane Proteins
  • MicroRNAs