microRNA100 inhibits self-renewal of breast cancer stem-like cells and breast tumor development
Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, lorsqu'il est surexprimé, le micro-ARN miR-100 réduit la capacité d'auto-renouvellement des cellules souches de cancer du sein
microRNAs are essential for self-renewal and differentiation of normal and malignant stem cells by regulating the expression of key stem cell regulatory genes. Here we report evidence implicating the microRNA100 (miR-100) in self-renewal of cancer stem-like cells (CSC). We found that miR-100 expression levels relate to the cellular differentiation state with lowest expression in cells displaying stem cell markers. Utilizing a tetracycline-inducible lentivirus to elevate expression of miR-100 in human cells, we found that increasing mir-100 levels decreased the production of breast CSCs. This effect was correlated with an inhibition of cancer cell proliferation in vitro and in mouse tumor xenografts due to attenuated expression of the CSC regulatory genes SMARCA5, SMARCD1 and BMPR2. Furthermore, miR-100 induction in breast CSC immediately upon their orthotopic implantation or intracardiac injection completely blocked tumor growth and metastasis formation. Clinically, we observed a significant association between miR-100 expression in breast cancer specimens and patient survival. Our results suggest that miR-100 is required to direct CSC self-renewal and differentiation.