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

Elife. 2014 Nov 18;3:e01977. doi: 10.7554/eLife.01977.

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.

Keywords: APC; WNT signaling pathway; breast cancer; cancer stem cells; cell biology; human; human biology; medicine; miR-142; miR-150; mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Argonaute Proteins / metabolism
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Cell Proliferation
  • Clone Cells
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperplasia
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Organoids / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Induced Silencing Complex / metabolism
  • Transcription, Genetic
  • Up-Regulation / genetics
  • Wnt Signaling Pathway* / genetics

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Argonaute Proteins
  • MIRN142 microRNA, human
  • MIRN150 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA-Induced Silencing Complex