Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis
Melatonin Regulates Breast Cancer Progression by the lnc010561/miR-30/FKBP3 Axis
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褪黑素通过 lnc010561/miR-30/FKBP3 轴调节乳腺癌进展
DOI：
10.1016/j.omtn.2019.12.019
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发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Xie, Xiaoming
中科院分区：
文献类型：
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作者：
Liu, Peng;Xie, Xinhua;Xie, Xiaoming
褪黑激素被认为可以减缓乳腺癌的生长。其分子机制可能涉及长链非编码RNA（lncRNA）。然而，褪黑激素如何影响乳腺癌中lncRNA的表达和功能知之甚少。我们使用微阵列来探索褪黑素处理的乳腺癌细胞中mRNA和lncRNA的表达谱。进行基因和基因组的京都百科全书（KEGG）和Reactome途径分析以鉴定褪黑激素处理后受改变的表达mRNA影响的信号传导途径。为探讨筛选出的差异表达mRNA和lncRNA在乳腺癌中的功能和机制，我们进行了一系列实验。我们发现，FK 506结合蛋白3（FKBP 3）和lnc 010561在褪黑激素处理的乳腺癌细胞下调。FKBP 3和lnc 010561的敲低抑制乳腺癌的增殖和侵袭，并诱导细胞凋亡。此外，lnc 010561和FKBP 3作为miR-30的竞争性内源RNA（ceRNA）发挥作用。我们的研究结果表明，褪黑激素通过lnc 010561/miR-30/FKBP 3轴调节乳腺癌的进展。因此，褪黑激素可以作为乳腺癌的抗癌策略。
Melatonin has been recognized to slow breast cancer growth. The molecular mechanisms may involve long non-coding RNAs (lncRNAs). However, little is known on how melatonin affects lncRNA expression and function in breast cancer. We used microarrays to explore the expression profile of mRNAs and lncRNAs in melatonin-treated breast cancer cells. Kyoto encyclopedia of genes and genomes (KEGG) and Reactome pathways analysis were performed to identify the signaling pathways affected by altered expressed mRNAs after melatonin treatment. To explore the functions and mechanisms of the selected differentially expressed mRNA and lncRNA in breast cancer, we performed a series of experiments. We found that FK506-binding protein 3 (FKBP3) and lnc010561 were downregulated in melatonin-treated breast cancer cells. Knockdown of FKBP3 and lnc010561 inhibited breast cancer proliferation and invasion, and induced apoptosis. Also, lnc010561 and FKBP3 functioned as competing endogenous RNAs (ceRNAs) for miR-30. Our findings suggested that melatonin regulated breast cancer progression by the lnc010561/miR-30/FKBP3 axis. Melatonin may, therefore, function as an anticancer strategy for breast cancer.