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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere01977
JournaleLife
Volume3
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway'. Together they form a unique fingerprint.

Cite this