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