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
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / metabolism
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Animals
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Antibiotics, Antineoplastic / pharmacology*
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Antibiotics, Antineoplastic / therapeutic use
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Breast Neoplasms / drug therapy
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Breast Neoplasms / genetics*
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Cell Proliferation / drug effects
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Cell Proliferation / genetics
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Down-Regulation / genetics
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Doxorubicin / pharmacology
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Doxorubicin / therapeutic use
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Drug Resistance, Neoplasm / genetics*
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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MCF-7 Cells
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Mice
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Mice, Nude
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MicroRNAs / agonists
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / metabolism*
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Neoplastic Stem Cells / drug effects
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RNA, Messenger / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Wnt1 Protein / genetics*
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Wnt1 Protein / metabolism
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Xenograft Model Antitumor Assays
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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Antibiotics, Antineoplastic
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MicroRNAs
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Mirn140 microRNA, human
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RNA, Messenger
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WNT1 protein, human
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Wnt1 Protein
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Doxorubicin