MicroRNA-206 attenuates the growth and angiogenesis in non-small cell lung cancer cells by blocking the 14-3-3ζ/STAT3/HIF-1α/VEGF signaling.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Angiogenesis is the major hallmark in NSCLC. So, further elucidation of molecular mechanisms underlying the angiogenesis of NSCLC is urgently needed. Here, we found that microRNA-206 (miR-206) decreased the angiogenic ability in NSCLC via inhibiting the 14-3-3ζ/STAT3/HIF-1α/VEGF pathway. Briefly, 14-3-3ζ bond with phosphorylated-STAT3, and in turn, elevated the expression of HIF-1α. Then, by enhancing the recruitment of HIF-1α to VEGF promoter, 14-3-3ζ increased the angiogenesis. However, miR-206 decreased the angiogenesis by targeting 14-3-3ζ, and inhibiting the STAT3/HIF-1α/VEGF pathway. In NSCLC cell xenograft model, either overexpression of miR-206 or inhibition of 14-3-3ζ inhibited the STAT3/HIF-1α/VEGF pathway and decreased the tumor growth and angiogenesis. Furthermore, there was a negative correlation between miR-206 and 14-3-3ζ in NSCLC specimens. NSCLC patients with low expressions of miR-206 but high expressions of 14-3-3ζ had the worst survival. Collectively, our findings provided the underlying mechanisms of miR-206/14-3-3ζ in tumor growth and angiogenesis, and implicated miR-206 and 14-3-3ζ as potential therapeutic targets for NSCLC.
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Dong
D
Xue
Department of Nutrition And Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China.
Ye
Y
Yang
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Yawei
Y
Liu
Department of Nutrition And Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China.
Peiwen
P
Wang
Department of Nutrition And Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yi
Y
Dai
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Qinqiang
Q
Liu
Department of Nutrition And Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China.
Lijun
L
Chen
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Jian
J
Shen
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Huanyu
H
Ju
Department of Nutrition and Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yuan
Y
Li
Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China.
Zhenguo
Z
Tan
D048948:14-3-3 Proteins / Q000378:metabolism; D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D048948:14-3-3 Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A
14-3-3ζ; angiogenesis; lung cancer; microRNA-206; signal transduction