Abstract
BackgroundMicroRNA (miRNA) are negative regulators of gene expression, capable of exerting pronounced influences upon the translation and stability of mRNA. They are potential regulators of normal mammary gland development and of the maintenance of mammary epithelial progenitor cells. This study was undertaken to determine the role of miR-30b on the establishment of a functional mouse mammary gland. miR-30b is a member of the miR-30 family, composed of 6 miRNA that are highly conserved in vertebrates. It has been suggested to play a role in the differentiation of several cell types.Methodology/Principal FindingsThe expression of miR-30b was found to be regulated during mammary gland development. Transgenic mice overexpressing miR-30b in mammary epithelial cells were used to investigate its role. During lactation, mammary histological analysis of the transgenic mice showed a reduction in the size of alveolar lumen, a defect of the lipid droplets and a growth defect of pups fed by transgenic females. Moreover some mammary epithelial differentiated structures persisted during involution, suggesting a delay in the process. The genes whose expression was affected by the overexpression of miR-30b were characterized by microarray analysis.Conclusion/SignificanceOur data suggests that miR-30b is important for the biology of the mammary gland and demonstrates that the deregulation of only one miRNA could affect lactation and involution.
Highlights
MicroRNA, endogenous small RNA (18–22 nt), are negative regulators of gene expression, capable of exerting pronounced influences upon the translation and stability of mRNA [1,2]. miRNA-mediated gene regulation is crucial for many biological processes such as cellular growth, cell differentiation, death or polarity [3]
The miR-30 family is highly conserved in Vertebrates, it is composed by 6 miRNA and it is organized in 3 clusters of two miRNA localized on 3 different chromosomes
It is regulated by estrogen in breast cancer cells [20], associated with mammary tumorigenesis and metastasis [21], and it is one of the 13 miRNA whose expression of which differs between inflammatory breast cancer (IBC) and non IBC [22]
Summary
MicroRNA (miRNA), endogenous small RNA (18–22 nt), are negative regulators of gene expression, capable of exerting pronounced influences upon the translation and stability of mRNA [1,2]. miRNA-mediated gene regulation is crucial for many biological processes such as cellular growth, cell differentiation, death or polarity [3]. Conclusion/Significance: Our data suggests that miR-30b is important for the biology of the mammary gland and demonstrates that the deregulation of only one miRNA could affect lactation and involution. We used transgenic mice overexpressing miR-30b to investigate its role in the development and differentiation of mammary epithelial cells in vivo and we show that miR-30b deregulation leads to an impairment of mammary gland structure and function during lactation and involution.
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