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MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4

  • Authors:
    • Xue Liang
    • Zhao Xu
    • Meng Yuan
    • Yue Zhang
    • Bo Zhao
    • Junqian Wang
    • Aixue Zhang
    • Guangping Li
  • View Affiliations / Copyright

    Affiliations: Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
    Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 967-975
    |
    Published online on: February 22, 2016
       https://doi.org/10.3892/ijmm.2016.2497
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Abstract

Programmed cell death 4 (PDCD4) is involved in a number of bioprocesses, such as apoptosis and inflammation. However, its regulatory mechanisms in atherosclerosis remain unclear. In this study, we investigated the role and mechanisms of action of PDCD4 in high-fat diet-induced atherosclerosis in mice and in foam cells (characteristic pathological cells in atherosclerotic lesions) derived from ox-LDL-stimulated macrophages. MicroRNA (miR)-16 was predicted to bind PDCD4 by bioinformatics analysis. In the mice with atherosclerosis and in the foam cells, PDCD4 protein expression (but not the mRNA expression) was enhanced, while that of miR‑16 was reduced. Transfection with miR‑16 mimic decreased the activity of a luciferase reporter containing the 3' untranslated region (3'UTR) of PDCD4 in the macrophage-derived foam cells. Conversely, treatment with miR‑16 inhibitor enhanced the luciferase activity. However, by introducing mutations in the predicted binding site located in the 3'UTR of PDCD4, the miR‑16 mimic and inhibitor were unable to alter the level of PDCD4, suggesting that miR‑16 is a direct negative regulator of PDCD4 in atherosclerosis. Furthermore, transfection wtih miR‑16 mimic and siRNA targeting PDCD4 suppressed the secretion and mRNA expression of pro-inflammatory factors, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF‑α), whereas it enhanced the secretion and mRNA expression of the anti-inflammatory factor, IL-10. Treatment with miR‑16 inhibitor exerted the opposite effects. In addition, the phosphorylation of p38 and extracellular signal-regulated kinase (ERK), and nuclear factor-κB (NF-κB) expression were altered by miR‑16. In conclusion, our data demonstrate that the targeting of PDCD4 by miR‑16 may suppress the activation of inflammatory macrophages though mitogen-activated protein kinase (MAPK) and NF-κB signaling in atherosclerosis; thus, PDCD4 may prove to be a potential therapeutic target in the treatment of atherosclerosis.
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Copy and paste a formatted citation
Spandidos Publications style
Liang X, Xu Z, Yuan M, Zhang Y, Zhao B, Wang J, Zhang A and Li G: MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4. Int J Mol Med 37: 967-975, 2016.
APA
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J. ... Li, G. (2016). MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4. International Journal of Molecular Medicine, 37, 967-975. https://doi.org/10.3892/ijmm.2016.2497
MLA
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J., Zhang, A., Li, G."MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4". International Journal of Molecular Medicine 37.4 (2016): 967-975.
Chicago
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J., Zhang, A., Li, G."MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4". International Journal of Molecular Medicine 37, no. 4 (2016): 967-975. https://doi.org/10.3892/ijmm.2016.2497
Copy and paste a formatted citation
x
Spandidos Publications style
Liang X, Xu Z, Yuan M, Zhang Y, Zhao B, Wang J, Zhang A and Li G: MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4. Int J Mol Med 37: 967-975, 2016.
APA
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J. ... Li, G. (2016). MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4. International Journal of Molecular Medicine, 37, 967-975. https://doi.org/10.3892/ijmm.2016.2497
MLA
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J., Zhang, A., Li, G."MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4". International Journal of Molecular Medicine 37.4 (2016): 967-975.
Chicago
Liang, X., Xu, Z., Yuan, M., Zhang, Y., Zhao, B., Wang, J., Zhang, A., Li, G."MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4". International Journal of Molecular Medicine 37, no. 4 (2016): 967-975. https://doi.org/10.3892/ijmm.2016.2497
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