miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A

摘要

Increasing evidence suggests that hsa-miR-126 (miR-126)is down-regulated in non-small cell lung cancer (NSCLC)cell lines and the restoration of miR-126 impairs tumorcell proliferation,migration,invasion,and survival by targeting specific molecules.Here,we reported for the first time that miR-126 was involved in regulating the response of NSCLC cells to cancer chemotherapy.After transfected A549 cells with miR-126 mimic or inhibitor,we found that an elevated level of miR-126 was significantly associated with a decreased half maximal inhibitory concentration of adriamycin (ADM) and vincristine,an increased accumulation of ADM,down-regulation of vascular endothelial growth factor A (VEGFA) and multidrug resistance-associated protein 1 (MRP1),andinactivation of the Akt signaling pathway.Furthermore,enhanced expression of miR-126 suppressed the growth of A549 xenograft and inhibited the expression of VEGFA and MRP1.miR-126 could efficiently down-regulate VEGFA expression through the interaction with the VEGFA 3'-untranslated region,whereas restoration of VEGFA could partially attenuate the suppression of MRP1 by miR-126.However,LY294002,an inhibitor of the PI3K/Akt signaling pathway,diminished this effect,suggesting that enhanced expression of miR-126 increased the sensitivity of NSCLC cells to anticancer agents through negative regulation of a VEGF/PI3K/Akt/MRP1signaling pathway.