miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1

Cancer Gene Ther. 2019 Mar;26(3-4):74-82. doi: 10.1038/s41417-018-0035-0. Epub 2018 Jul 22.


MicroRNAs (miRNAs) are a group of small non-coding single-stranded RNAs molecules, the dysregulation of which plays a critical role in the initiation and biological progression of malignancies. The current study demonstrated that miR-140-5p was frequently downregulated in breast cancer stem cells (BCSCs), and miR-140-5p mimics could inhibit the proliferation of BCSCs. Moreover, Wnt1 was a direct target of miR-140-5p, as was proved by luciferase reporter assays. miR-140-5p mimics could downregulate the wnt1 mRNA and protein levels in MCF-7 and MDA-MB-231 cells. Furthermore, miR-140 mimics could enhance the sensitivity of BCSCs to doxorubicin (Dox) through the Wnt1/ABCB1 pathway both in vitro and vivo. Our findings have presented a novel miRNA-mediated regulatory network for BCSCs, which may provide a potential therapeutic target for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / drug effects
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Wnt1 Protein / genetics*
  • Wnt1 Protein / metabolism
  • Xenograft Model Antitumor Assays


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antibiotics, Antineoplastic
  • MicroRNAs
  • Mirn140 microRNA, human
  • RNA, Messenger
  • WNT1 protein, human
  • Wnt1 Protein
  • Doxorubicin