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

  • Authors:
    • Yue Li
    • Long Zhao
    • Yafei Qi
    • Xianghong Yang
  • View Affiliations

  • Published online on: April 16, 2019     https://doi.org/10.3892/mmr.2019.10170
  • Pages: 4935-4945
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Abstract

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‑1α 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‑1α signaling cascade was examined. It was demonstrated that miR‑214 mimics upregulated the expression of hypoxia‑inducible factor (HIF)‑1α, 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‑1α, MMP2 and VEGF expression. ING4 overexpression downregulated HIF‑1α and its targets MMP2 and VEGF, while ING4 siRNA upregulated HIF‑1α, MMP2 and VEGF. In conclusion, it was demonstrated that miR‑214 targeted ING4 in lung cancer cells, and upregulated the HIF‑1α 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.

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APA
Li, Y., Zhao, L., Qi, Y., & Yang, X. (2019). MicroRNA‑214 upregulates HIF‑1α and VEGF by targeting ING4 in lung cancer cells. Molecular Medicine Reports, 19, 4935-4945. https://doi.org/10.3892/mmr.2019.10170
MLA
Li, Y., Zhao, L., Qi, Y., Yang, X."MicroRNA‑214 upregulates HIF‑1α and VEGF by targeting ING4 in lung cancer cells". Molecular Medicine Reports 19.6 (2019): 4935-4945.
Chicago
Li, Y., Zhao, L., Qi, Y., Yang, X."MicroRNA‑214 upregulates HIF‑1α and VEGF by targeting ING4 in lung cancer cells". Molecular Medicine Reports 19, no. 6 (2019): 4935-4945. https://doi.org/10.3892/mmr.2019.10170