title: miR-126 enhances the sensitivity of non-small cell lung cancer cells to anticancer agents by targeting vascular endothelial growth factor A.
abstract: 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 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), 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 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/MRP1 signaling pathway.
authors.affiliation: The Affiliated People's Hospital,  Jiangsu University, Zhenjiang 212001,  China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Lulu
authors.initials: L
authors.lastname: Long
authors.forename: Lulu
authors.initials: L
authors.lastname: Hui
authors.forename: Haining
authors.initials: H
authors.lastname: Chen
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Huiling
authors.initials: H
authors.lastname: Shen
authors.forename: Wenlin
authors.initials: W
authors.lastname: Xu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D035683:MicroRNAs / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics*; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D002867:Chromones; D004317:Doxorubicin; D035683:MicroRNAs; D009025:Morpholines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051057:Proto-Oncogene Proteins c-akt; D042461:Vascular Endothelial Growth Factor A; D014750:Vincristine; C527111:MIRN126 microRNA, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C421109:multidrug resistance-associated protein 1