Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer
Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer
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DOI：
10.1038/s41419-020-02981-1
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发表时间：
2020-09-15
影响因子：
9
通讯作者：
Ma, Xuelei
中科院分区：
文献类型：
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作者：
Du, Peixin;Zeng, Hao;Ma, Xuelei
慢性应激可通过交感神经系统的持续激活诱导肿瘤转移，但其细胞机制尚不清楚。本研究旨在探讨慢性应激对肿瘤转移的负面影响。转录组测序分析提示，在慢性应激条件下，miR-337-3p下调激活STAT3信号通路可能是诱导癌细胞上皮向间充质转化(EMT)、促进转移的潜在机制。我们还在进一步的实验中验证了这一生物过程。在体内外，miR-337-3p的表达下调E-钙粘蛋白的表达，上调波形蛋白的表达。MiR-337-3p直接靶向参与肿瘤转移调控的信号转导通路STAT3。以上结果提示，miR-337-3p/STAT3轴的激活可能是慢性应激下乳腺癌转移增加的潜在途径。
Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.