miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway
oleh: Taichi Isobe, Shigeo Hisamori, Daniel J Hogan, Maider Zabala, David G Hendrickson, Piero Dalerba, Shang Cai, Ferenc Scheeren, Angera H Kuo, Shaheen S Sikandar, Jessica S Lam, Dalong Qian, Frederick M Dirbas, George Somlo, Kaiqin Lao, Patrick O Brown, Michael F Clarke, Yohei Shimono
| Format: | Article |
|---|---|
| Diterbitkan: | eLife Sciences Publications Ltd 2014-11-01 |
Deskripsi
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.