miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1
miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1
复制标题
miR-140-5p通过靶向Wnt1抑制乳腺癌干细胞增殖并增强阿霉素对乳腺癌干细胞的疗效
DOI：
10.1038/s41417-018-0035-0
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发表时间：
2019-03-01
影响因子：
6.4
通讯作者：
Mao, Jun
中科院分区：
文献类型：
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作者：
Wu, Dawei;Zhang, Jun;Mao, Jun
microRNA（miRNAs）是一类非编码的单链小RNA分子，其调控异常在恶性肿瘤的发生和生物学进展中起重要作用。目前的研究表明，miR-140- 5 p在乳腺癌干细胞（BCSC）中经常下调，miR-140- 5 p模拟物可以抑制BCSC的增殖。此外，Wnt 1是miR-140- 5 p的直接靶点，如荧光素酶报告基因测定所证明的。miR-140- 5 p模拟物可下调MCF-7和MDA-MB-231细胞中wnt 1的mRNA和蛋白水平。此外，miR-140模拟物可以通过Wnt 1/ABCB 1途径增强BCSCs对阿霉素（Dox）的敏感性。我们的研究结果提出了一种新的miRNA介导的BCSC调控网络，这可能为乳腺癌提供潜在的治疗靶点。
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.