Open Access

Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis

  • Authors:
    • Zhang-Jian Yang
    • Rong Liu
    • Xiao-Jian Han
    • Cheng-Lin Qiu
    • Guan-Lin Dong
    • Zi-Qin Liu
    • Li-Hua Liu
    • Yan Luo
    • Li-Ping Jiang
  • View Affiliations

  • Published online on: March 8, 2023     https://doi.org/10.3892/mmr.2023.12977
  • Article Number: 90
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long noncoding RNAs (lncRNAs) are related to the development of atherosclerosis (AS). However, the role of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tumor necrosis factor‑α (TNF‑α)‑induced rat aortic endothelial cell (RAOEC) pyroptosis, as well as the underlying mechanisms, remain unclear. RAOEC morphology was assessed using an inverted microscope. The mRNA and/or protein expression levels of MALAT1, microRNA(miR)‑30c‑5p and connexin 43 (Cx43) were assessed using reverse transcription‑quantitative PCR (RT‑qPCR) and/or western blotting, respectively. The relationships among these molecules were validated by dual‑luciferase reporter assays. Biological functions, such as LDH release, pyroptosis‑associated protein levels and the proportion of PI‑positive cells, were evaluated using a LDH assay kit, western blotting and Hoechst 33342/PI staining, respectively. The present study demonstrated that compared with the control group, the mRNA expression levels of MALAT1 and protein expression levels of Cx43 were significantly up‑regulated, whereas miR‑30c‑5p mRNA expressions levels were significantly decreased in TNF‑α‑treated RAOEC pyroptosis. Knockdown of MALAT1 or Cx43 significantly attenuated the increase in LDH release, pyroptosis‑associated protein expression and PI‑positive cell numbers among RAOEC treated using TNF‑α, whereas an miR‑30c‑5p mimic exerted the opposite effect. Furthermore, miR‑30c‑5p was demonstrated to be a negative regulator of MALAT1 and could also target Cx43. Finally, co‑transfection with siMALAT1 and miR‑30c‑5p inhibitor could attenuate the protective effect of MALAT1 knockdown against TNF‑α‑mediated RAOEC pyroptosis by upregulation of Cx43 expression. In conclusion, MALAT1 might serve an important role in TNF‑α‑mediated RAOEC pyroptosis by regulating the miR‑30c‑5p/Cx43 axis, which would provide a potential novel diagnostic and therapeutic target for AS.
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April-2023
Volume 27 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Yang Z, Liu R, Han X, Qiu C, Dong G, Liu Z, Liu L, Luo Y and Jiang L: Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis. Mol Med Rep 27: 90, 2023.
APA
Yang, Z., Liu, R., Han, X., Qiu, C., Dong, G., Liu, Z. ... Jiang, L. (2023). Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis. Molecular Medicine Reports, 27, 90. https://doi.org/10.3892/mmr.2023.12977
MLA
Yang, Z., Liu, R., Han, X., Qiu, C., Dong, G., Liu, Z., Liu, L., Luo, Y., Jiang, L."Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis". Molecular Medicine Reports 27.4 (2023): 90.
Chicago
Yang, Z., Liu, R., Han, X., Qiu, C., Dong, G., Liu, Z., Liu, L., Luo, Y., Jiang, L."Knockdown of the long non‑coding RNA MALAT1 ameliorates TNF‑α‑mediated endothelial cell pyroptosis via the miR‑30c‑5p/Cx43 axis". Molecular Medicine Reports 27, no. 4 (2023): 90. https://doi.org/10.3892/mmr.2023.12977