MiR-206 inhibits HGF-induced epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via c-Met /PI3k/ Akt/mTOR pathway

// Qing-yong Chen 1, * , De-min Jiao 1, * , Yu-quan Wu 2 , Jun Chen 1 , Jian Wang 1 , Xia-li Tang 1 , Hao Mou 1 , Hui-zhen Hu 1 , Jia Song 1 , Jie Yan 1 , Li-jun Wu 1 , Jianyan Chen 3 , Zhiwei Wang 4, 5 1 Department of Respiratory Disease, The 117 th Hospital of PLA, Zhejiang, China 2 Department of Oncology, The 117 th Hospital of PLA, Zhejiang, China 3 Department of Anesthesiology, Shenzhen Baoan Hospital Affiliated to Southern Medical University, Guangdong, China 4 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 5 The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China * These authors contribute equally to this work Correspondence to: Jianyan Chen, e-mail: chenjianyan@yahoo.com Zhiwei Wang, e-mail: zwang6@bidmc.harvard.edu Qing-yong Chen, e-mail: cqyong117@163.com Keywords: miR-206, HGF, epithelial-mesenchymal transition, angiogenesis, lung cancer Received: November 05, 2015      Accepted: February 9, 2016      Published: February 22, 2016 ABSTRACT MiR-206 is low expression in lung cancers and associated with cancer metastasis. However, the roles of miR-206 in epithelial-mesenchymal transition (EMT) and angiogenesis in lung cancer remain unknown. In this study, we find that hepatocyte growth factor (HGF) induces EMT, invasion and migration in A549 and 95D lung cancer cells, and these processes could be markedly inhibited by miR-206 overexpression. Moreover, we demonstrate that miR-206 directly targets c-Met and inhibits its downstream PI3k/Akt/mTOR signaling pathway. In contrast, miR-206 inhibitors promote the expression of c-Met and activate the PI3k/Akt/mTOR signaling, and this effect could be attenuated by the PI3K inhibitor. Moreover, c-Met overexpression assay further confirms the significant inhibitory effect of miR-206 on HGF-induced EMT, cell migration and invasion. Notably, we also find that miR-206 effectively inhibits HGF-induced tube formation and migration of human umbilical vein endothelial cells (HUVECs), and the mechanism is also related to inhibition of PI3k/Akt/mTOR signaling. Finally, we reveal the inhibitory effect of miR-206 on EMT and angiogenesis in xenograft tumor mice model. Taken together, miR-206 inhibits HGF-induced EMT and angiogenesis in lung cancer by suppressing c-Met/PI3k/Akt/mTOR signaling. Therefore, miR-206 might be a potential target for the therapeutic strategy against EMT and angiogenesis of lung cancer.