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Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps

  • Authors:
    • Zhuohui Liu
    • Haoyu Liu
    • Deshun Yu
    • Jingyu Gao
    • Biao Ruan
    • Ruiqing Long

  • View Affiliations

  • Published online on: May 12, 2021     https://doi.org/10.3892/ijmm.2021.4959
  • Article Number: 126

  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Matrix metalloproteinase (MMP)‑9 is a key enzyme responsible for extracellular matrix degradation and contributes to the progressive histological changes observed in lower respiratory tract infections. Integrin β1 and α‑tubulin are potential MMP‑9‑interacting proteins, and microRNA (miR)‑29b‑3p can regulate MMP‑9 expression. MMP‑9 is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNPs), regardless of its effects on miR‑29b‑3p, integrin β1 and α‑tubulin expression. In the present study, samples from 100 patients with CRSwNPs were examined via reverse transcription‑quantitative PCR to assess the mRNA expression of miR‑29b‑3p, and western blotting was performed to assess the protein expression of MMP‑2, MMP‑9, acetyl‑α‑tubulin, integrin β1 and tissue inhibitor of metalloproteinase 1 (TIMP‑1). A dual‑luciferase reporter assay was used to verify the direct binding of miR‑29b‑3p and MMP‑2/MMP‑9. Co‑immunoprecipitation (Co‑IP) and GST pull‑down assays showed that integrin β1 and α‑tubulin were MMP‑9‑interacting proteins. Cell viability, apoptosis and inflammatory cytokine levels were determined via a Cell Counting Kit‑8 assay, flow cytometry and ELISA, respectively. miR‑29b‑3p expression was found to be positively correlated with MMP‑2 and MMP‑9 expression. Whereas, TIMP‑1 expression was negatively correlated with MMP‑2 and MMP‑9 expression. The dual‑luciferase assay revealed that miR‑29b‑3p targeted the 3' untranslated region of MMP‑2/MMP‑9. The Co‑IP and GST pull‑down assays showed that MMP‑9 could directly bind to integrin β1 and indirectly bind to α‑tubulin. Finally, the overexpression of miR‑29b‑3p decreased the expression of MMP‑9 and increased the levels of acetyl‑α‑tubulin. By contrast, the knockdown of miR‑29b‑3p increased the expression of MMP‑9 and decreased the levels of acetyl‑α‑tubulin. Additionally, MMP‑9 expression was found to be negatively correlated with acetyl‑α‑tubulin expression. Of note, the expression of integrin β1 did not change following the overexpression and knockdown of MMP‑9. Finally, the overexpression of miR‑29b‑3p not only decreased MMP‑9 expression, but also alleviated lipopolysaccharide‑induced inflammation in NP69 cells. The results showed that the downregulation of miR‑29b‑3p promoted α‑tubulin deacetylation by increasing the number of MMP‑9‑integrin β1 complexes in CRSwNPs, thus targeting miR‑29b‑3p/MMP‑9 may be a potential novel strategy for the clinical treatment of CRSwNPs.
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July-2021
Volume 48 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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  • Impact Factor: 5.7
  • Ranked Medicine Research and Experimental
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  • CiteScore: 12.3
  • CiteScore Rank: Q1: #28/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 1.022
  • SCImago Journal Rank (SJR): 1.167
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Spandidos Publications style
Liu Z, Liu H, Yu D, Gao J, Ruan B and Long R: Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps. Int J Mol Med 48: 126, 2021
APA
Liu, Z., Liu, H., Yu, D., Gao, J., Ruan, B., & Long, R. (2021). Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps. International Journal of Molecular Medicine, 48, 126. https://doi.org/10.3892/ijmm.2021.4959
MLA
Liu, Z., Liu, H., Yu, D., Gao, J., Ruan, B., Long, R."Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps". International Journal of Molecular Medicine 48.1 (2021): 126.
Chicago
Liu, Z., Liu, H., Yu, D., Gao, J., Ruan, B., Long, R."Downregulation of miR‑29b‑3p promotes α‑tubulin deacetylation by targeting the interaction of matrix metalloproteinase‑9 with integrin β1 in nasal polyps". International Journal of Molecular Medicine 48, no. 1 (2021): 126. https://doi.org/10.3892/ijmm.2021.4959