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

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 tumor cell proliferation, migration, invasion, and survival by tar- geting 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 asso- ciated with a decreased half maximal inhibitory concen- tration of adriamycin （ADM） and vincristine, an increased accumulation of ADM, down-regulation of vas- cular endothelial growth factor A （VEGFA） and multi- drug resistance-associated protein 1 （MRP1）, and inactivation of the Akt signaling pathway. Furthermore, enhanced expression of miR-126 suppressed the growth of A549 xenograft and inhibited the expression of VEGFA and MRPI. 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 ceils to anticancer agents through negative regulation of a VEGF/PI3K/Akt/MRP1 signaling pathway.