MicroRNA-206 attenuates the growth and angiogenesis in non-small cell lung cancer cells by blocking the 14-3-3z/STAT3/HIF-1a/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 14-3-3z/STAT3/HIF-1a/VEGF pathway. Briefly, 143-3z bond with phosphorylated-STAT3, and in turn, elevated the expression of HIF-1a. Then, by enhancing the recruitment of HIF-1a to VEGF promoter, 14-3-3z increased the angiogenesis. However, miR-206 decreased the angiogenesis by targeting 14-33z, and inhibiting the STAT3/HIF-1a/VEGF pathway. In NSCLC cell xenograft model, either overexpression of miR-206 or inhibition of 14-3-3z inhibited the STAT3/HIF1a/VEGF pathway and decreased the tumor growth and angiogenesis. Furthermore, there was a negative correlation between miR-206 and 14-3-3z in NSCLC specimens. NSCLC patients with low expressions of miR-206 but high expressions of 14-3-3z had the worst survival. Collectively, our findings provided the underlying mechanisms of miR-206/14-3-3z in tumor growth and angiogenesis, and implicated miR-206 and 14-3-3z as potential therapeutic targets for NSCLC.