MiR-206 inhibits HGF-induced epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via c-Met /PI3k/ Akt/mTOR pathway
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Qing-yong Chen1,*, De-min Jiao1,*, Yu-quan Wu2, Jun Chen1, Jian Wang1, Xia-li Tang1, Hao Mou1, Hui-zhen Hu1, Jia Song1, Jie Yan1, Li-jun Wu1, Jianyan Chen3, Zhiwei Wang4,5
1Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China
2Department of Oncology, The 117th Hospital of PLA, Zhejiang, China
3Department of Anesthesiology, Shenzhen Baoan Hospital Affiliated to Southern Medical University, Guangdong, China
4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
5The 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
Jianyan Chen, e-mail: firstname.lastname@example.org
Zhiwei Wang, e-mail: email@example.com
Qing-yong Chen, e-mail: firstname.lastname@example.org
Keywords: miR-206, HGF, epithelial-mesenchymal transition, angiogenesis, lung cancer
Received: November 05, 2015 Accepted: February 9, 2016 Published: February 22, 2016
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.
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