MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells
1 Epigenetics Group. International Agency for Research on Cancer (IARC), 150 rue Albert-Thomas, Lyon, 69008, France
2 Faculty of Health Sciences, University of Ottawa, Ottawa, K1H 8M5, Canada
3 Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), 150 rue Albert-Thomas, Lyon, 69008, France
4 Ohio State University, 1082 Biomedical Research Tower, 460 W 12th Ave, Columbus, OH 43210, USA
5 Epigenetics Group, International Agency for Research on Cancer (IARC), 150 cours Albert-Thomas, Lyon cedex 08, 69372, France
BMC Genomics 2013, 14:139 doi:10.1186/1471-2164-14-139Published: 28 February 2013
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.
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.
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.