Open Access

Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension

  • Authors:
    • Dapeng Wang
    • Hongyang Xu
    • Bo Wu
    • Shuyun Jiang
    • Hong Pan
    • Ruilan Wang
    • Jingyu Chen
  • View Affiliations

  • Published online on: June 25, 2019     https://doi.org/10.3892/ijmm.2019.4256
  • Pages: 871-884
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have demonstrated that long non‑coding RNA (lncRNA) is involved in vascular remodeling. The metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA is associated with the proliferation and migration of vascular smooth muscle and endothelial cells; however, its biological role in pulmonary artery hypertension (PAH) is currently unclear. The aim of the present study was to investigate the post‑transcriptional regulation of MALAT1 in human pulmonary artery smooth muscle cells (HPASMCs). The results revealed that MALAT1 expression levels were significantly upregulated in the pulmonary arteries (PAs) and HPASMCs obtained from patients with PAH compared with adjacent normal PA tissues and HPASMCs. Knockdown of MALAT1 suppressed the viability and proliferation of HPASMCs and prevented cells entering the G0/G1 cell cycle phase. MALAT1 overexpression exerted the opposite effects. Bioinformatics analysis predicted complementary binding of hsa‑microRNA (miR)‑124‑3p.1 with the 3'‑untranslated region of MALAT1. Luciferase reporter assays and RNA immunoprecipitation experiments demonstrated molecular binding between MALAT1 and hsa‑miR‑124‑3p.1. This resulted in the formation of an RNA‑induced silencing complex. In addition, Kruppel‑like factor 5 (KLF5) was confirmed to be a target gene of MALAT1/hsa‑miR‑124‑3p.1. MALAT1 silencing did not inhibit the proliferation and migration of HPASMCs following knockdown of hsa‑miR‑124‑3p.1. In addition, MALAT1 knockdown was demonstrated to attenuate the expression of KLF5. Following MALAT1 knockdown, the expression level of KLF5 was rescued by inhibition of hsa‑miR‑124‑3p.1 expression. The results of the current study indicate that the MALAT1/hsa‑miR‑124‑3p.1/KLF5 axis may serve a key role in HPASMCs. In addition, the results contribute to what is known regarding the role of MALAT1 in PAH development and provide a novel theoretical basis for the development of new therapeutic interventions for patients with PAH.

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September 2019
Volume 44 Issue 3

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

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Copy and paste a formatted citation
APA
Wang, D., Xu, H., Wu, B., Jiang, S., Pan, H., Wang, R., & Chen, J. (2019). Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension. International Journal of Molecular Medicine, 44, 871-884. https://doi.org/10.3892/ijmm.2019.4256
MLA
Wang, D., Xu, H., Wu, B., Jiang, S., Pan, H., Wang, R., Chen, J."Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension". International Journal of Molecular Medicine 44.3 (2019): 871-884.
Chicago
Wang, D., Xu, H., Wu, B., Jiang, S., Pan, H., Wang, R., Chen, J."Long non‑coding RNA MALAT1 sponges miR‑124‑3p.1/KLF5 to promote pulmonary vascular remodeling and cell cycle progression of pulmonary artery hypertension". International Journal of Molecular Medicine 44, no. 3 (2019): 871-884. https://doi.org/10.3892/ijmm.2019.4256