Doxycycline inhibits breast cancer EMT and metastasis through PAR-1/NF-&#x03BA;B/miR-17/E-cadherin pathway

Weilong Zhong; Shuang Chen; Yuan Qin; Heng Zhang; Hongzhi Wang; Jing Meng; Longcong Huai; Qiang Zhang; Tingting Yin; Yueyang Lei; Jingxia Han; Lingfei He; Bo Sun; Huijuan Liu; Yanrong Liu; Honggang Zhou; Tao Sun; Cheng Yang

doi:10.18632/oncotarget.20418

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Research Papers:

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

Weilong Zhong, Shuang Chen, Yuan Qin, Heng Zhang, Hongzhi Wang, Jing Meng, Longcong Huai, Qiang Zhang, Tingting Yin, Yueyang Lei, Jingxia Han, Lingfei He, Bo Sun, Huijuan Liu, Yanrong Liu, Honggang Zhou, Tao Sun _ and Cheng Yang

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Oncotarget. 2017; 8:104855-104866. https://doi.org/10.18632/oncotarget.20418

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Abstract

Weilong Zhong1,*, Shuang Chen2,*, Yuan Qin1,*, Heng Zhang1,*, Hongzhi Wang1, Jing Meng1, Longcong Huai1, Qiang Zhang1, Tingting Yin1, Yueyang Lei1, Jingxia Han1, Lingfei He1, Bo Sun2, Huijuan Liu2, Yanrong Liu2, Honggang Zhou1,2, Tao Sun1,2 and Cheng Yang1,2

1State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300000, China

2Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, 300000, China

*These authors have contributed equally to this work

Correspondence to:

Tao Sun, email: [email protected]

Cheng Yang, email: [email protected]

Keywords: doxycycline; miR-17; EMT; GPCR; NF-κB

Received: March 14, 2017 Accepted: June 27, 2017 Published: August 24, 2017

ABSTRACT

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.

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Research Papers:

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

Abstract