miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway

T Isobe, S Hisamori, DJ Hogan, M Zabala… - Elife, 2014 - elifesciences.org
T Isobe, S Hisamori, DJ Hogan, M Zabala, DG Hendrickson, P Dalerba, S Cai, F Scheeren
Elife, 2014elifesciences.org
MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We
previously reported that miR-142 and miR-150 are upregulated in human breast cancer
stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study,
we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing
complex, activates the canonical WNT signaling pathway in an APC-suppression dependent
manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR …
MicroRNAs (miRNAs) are important regulators of stem and progenitor cell functions. We previously reported that miR-142 and miR-150 are upregulated in human breast cancer stem cells (BCSCs) as compared to the non-tumorigenic breast cancer cells. In this study, we report that miR-142 efficiently recruits the APC mRNA to an RNA-induced silencing complex, activates the canonical WNT signaling pathway in an APC-suppression dependent manner, and activates the expression of miR-150. Enforced expression of miR-142 or miR-150 in normal mouse mammary stem cells resulted in the regeneration of hyperproliferative mammary glands in vivo. Knockdown of endogenous miR-142 effectively suppressed organoid formation by BCSCs and slowed tumor growth initiated by human BCSCs in vivo. These results suggest that in some tumors, miR-142 regulates the properties of BCSCs at least in part by activating the WNT signaling pathway and miR-150 expression.
DOI: http://dx.doi.org/10.7554/eLife.01977.001
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