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

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 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. Overall design: Tumors removed from 4T1 tumor bearing mice suffered chronic restraint stress 2 hours a day for consecutive 28 days were labeled as stress group. Tumors removed from 4T1 tumor bearing mice with no treatment were used as control group. There were three samples in stress and control group respectively.

本研究旨在探讨慢性应激的肿瘤转移相关负面影响。转录组测序分析结果显示，miR-337-3p介导的STAT3信号通路激活，或为慢性应激下诱导癌细胞上皮间质转化（Epithelial to Mesenchymal Transition, EMT）并促进肿瘤转移的潜在机制。我们通过后续实验验证了这一生物学过程：体内外实验均证实，下调miR-337-3p可降低E-钙粘蛋白（E-cadherin）的表达并上调波形蛋白（vimentin）的表达。STAT3及其相关信号通路参与肿瘤转移调控，且STAT3是miR-337-3p的直接靶标。
实验设计如下：应激组的4T1荷瘤小鼠每日接受2小时慢性束缚应激，连续28天后摘除肿瘤；对照组为未接受任何处理的4T1荷瘤小鼠，直接摘除肿瘤。两组各设置3个生物学重复样本。