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
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Dong Xue1,*, Ye Yang2,*, Yawei Liu1,*, Peiwen Wang2,*, Yi Dai2, Qinqiang Liu1, Lijun Chen2, Jian Shen1, Huanyu Ju1, Yuan Li2, Zhenguo Tan1
1Department of Surgery, The Second Affiliated Hospital, Nanjing Medical University, Nanjing 211166, China
2Department of Nutrition And Food Hygiene, School Of Public Health, Nanjing Medical University, Nanjing 211166, China
*These authors have contributed equally to this work
Yuan Li, email: email@example.com
Zhenguo Tan, email: firstname.lastname@example.org
Keywords: lung cancer, microRNA-206, 14-3-3ζ, angiogenesis, signal transduction
Received: August 11, 2016 Accepted: October 14, 2016 Published: October 28, 2016
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.
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