title: MiR-206 inhibits HGF-induced epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via c-Met /PI3k/Akt/mTOR pathway.
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.
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Qing-yong
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: De-min
authors.initials: DM
authors.lastname: Jiao
authors.affiliation: Department of Oncology, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Yu-quan
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Xia-li
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Mou
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Hui-zhen
authors.initials: HZ
authors.lastname: Hu
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Respiratory Disease, The 117th Hospital of PLA, Zhejiang, China.
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Shenzhen Baoan Hospital Affiliated to Southern Medical University, Guangdong, China.
authors.forename: Jianyan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D017228:Hepatocyte Growth Factor; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D058570:TOR Serine-Threonine Kinases; C066855:HGF protein, human; C546087:MIRN206 microRNA, human; C546842:MTOR protein, human; C491743:MET protein, human
keywords: HGF; angiogenesis; epithelial-mesenchymal transition; lung cancer; miR-206