MicroRNA-206 attenuates the growth and angiogenesis in non-small cell lung cancer cells by blocking the 14-3-3?/STAT3/HIF-1?/VEGF signaling.

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

SUBMITTER: Xue D 

PROVIDER: S-EPMC5346752 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature