Doxycycline inhibits breast cancer EMT and metastasis through PAR-1/NF-κB/miR-17/E-cadherin pathway

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.