MicroRNA-214 upregulates HIF-1α and VEGF by targeting ING4 in lung cancer cells

Previous reports have indicated a potential link between microRNA (miR)-214 and hypoxia. In the present study, the biological functions and potential mechanisms of miR-214 were determined, as well as its correlation with HIF-1 alpha signaling in non-small cell lung cancer (NSCLC) cells. Quantitative polymerase chain reaction revealed that miR-214 expression was upregulated in lung cancer tissues compared with adjacent normal tissues. miR-214 mimics were transfected into A549 cells, and MTT, colony formation, invasion and wound healing assays were performed. It was demonstrated that miR-214 mimic transfection promoted the invasion, proliferation and migration of A549 cells. Furthermore, miR-214 inhibitor transfection decreased H1299 cell invasion, proliferation and migration. Next, the association between miR-214 expression and the HIF-1 alpha signaling cascade was examined. It was demonstrated that miR-214 mimics upregulated the expression of hypoxia-inducible factor (HIF)-1 alpha, vascular endothelial growth factor (VEGF), adenylate kinase 3 and matrix metalloproteinase (MMP)2, whereas miR-214 inhibitor downregulated the expression of these factors. Using prediction software, it was demonstrated that tumor suppressor ING4 was a target of miR-214. A luciferase reporter assay confirmed that ING4 was a direct target of miR-214. There was a negative correlation between ING4 and miR-214 expression in lung cancer tissues. In addition, ING4 siRNA and plasmid was transfected into cells in order to validate its effect on HIF-1 alpha, MMP2 and VEGF expression. ING4 overexpression downregulated HIF-1 alpha and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF-1 alpha, MMP2 and VEGF. In conclusion, it was demonstrated that miR-214 targeted ING4 in lung cancer cells, and upregulated the HIF-1 alpha cascade, leading to MMP2 and VEGF upregulation. This approach may help to clarify the role of miRNA in non-small lung cancer and may be a new therapeutic target for non-small lung cancer.