Doxycycline inhibits breast cancer EMT and metastasis through PAR-1/NF-κB/miR-17/E-cadherin pathway.
Doxycycline inhibits breast cancer EMT and metastasis through PAR-1/NF-κB/miR-17/E-cadherin pathway.
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强力霉素通过PAR-1/NF-κB/miR-17/E-cadherin通路抑制乳腺癌EMT和转移
DOI：
10.18632/oncotarget.20418
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发表时间：
2017-12-01
期刊：
影响因子：
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通讯作者：
Yang C
中科院分区：
文献类型：
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作者：
Zhong W;Chen S;Qin Y;Zhang H;Wang H;Meng J;Huai L;Zhang Q;Yin T;Lei Y;Han J;He L;Sun B;Liu H;Liu Y;Zhou H;Sun T;Yang C
强力霉素在癌症治疗中显示出高效率。然而，分子机制知之甚少。在我们以前的研究中，发现强力霉素通过直接靶向蛋白酶激活受体1（PAR 1）来抑制肿瘤进展。在这项研究中，发现microRNA参与PAR 1介导的多西环素抗肿瘤作用。在这些miRNAs中，发现miR-17在体内和体外均促进乳腺癌细胞转移。此外，miR-17可以逆转部分强力霉素对乳腺癌的抑制作用。采用荧光素酶和染色质免疫沉淀分析，发现核因子-κ B（NF-κB）结合miR-17启动子。此外，E-cadherin被鉴定为miR-17的靶基因。这些结果表明，miR-17可以通过靶向E-cadherin抵抗强力霉素对乳腺癌上皮间质转化（EMT）的抑制作用。
Doxycycline displays high efficiency for cancer therapy. However, the molecular mechanism is poorly understood. In our previous study, doxycycline was found to suppress tumor progression by directly targeting proteinase-activated receptor 1 (PAR1). In this study, microRNAs were found to be involved in PAR1-mediated anti-tumor effects of doxycycline. Among these miRNAs, miR-17 was found to promote breast cancer cell metastasis both in vivo and in vitro. Moreover, miR-17 could reverse partial doxycycline inhibition effects on breast cancer. Employing luciferase and chromatin immunoprecipitation assays, nuclear factor-kappaB (NF-κB) was found to bind miR-17 promoters. Furthermore, E-cadherin was identified as the target gene of miR-17. These results showed that miR-17 can resist the inhibitory effects of doxycycline on breast cancer epithelial–mesenchymal transformation (EMT) by targeting E-cadherin.