Long non‑coding RNA NEAT1 promotes pulmonary fibrosis by regulating the microRNA‑455‑3p/SMAD3 axis

Liu,Yuan; Lu,Fu-Ai; Wang,Le; Wang,Yong-Fu; Wu,Chun-Feng

doi:10.3892/mmr.2021.11857

Long non‑coding RNA NEAT1 promotes pulmonary fibrosis by regulating the microRNA‑455‑3p/SMAD3 axis

Authors:
- Yuan Liu
- Fu-Ai Lu
- Le Wang
- Yong-Fu Wang
- Chun-Feng Wu
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Affiliations: Department of Rheumatology, Liuzhou People's Hospital, Liuzhou, Guangxi Autonomous Region 545006, P.R. China, Department of Rheumatology, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
Published online on: January 20, 2021 https://doi.org/10.3892/mmr.2021.11857
Article Number: 218
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pulmonary fibrosis is an excessive repair response to tissue damage, triggering hyperplasia of fibrotic connective tissues; however, there is no effective treatment in a clinical setting. The purpose of the present study was to investigate the roles of long non‑coding RNA nuclear enriched abundant transcript 1 (NEAT1) and microRNA‑455‑3p (miR‑455‑3p) were investigated in pulmonary fibrosis. In this study, the mRNA expression levels of NEAT1, miR‑455‑3p and SMAD3 in the HPAEpiC alveolar and BEAS‑2B bronchial epithelial cell lines were determined using reverse transcription‑quantitative PCR, while the markers of epithelial‑mesenchymal transformation (EMT) and collagen production were determined using western blot analysis. A wound healing assay was performed to evaluate the migratory ability of the HPAEpiC and BEAS‑2B cell lines. The interactions between NEAT1 and miR‑455‑3p or SMAD3 and miR‑455‑3p were validated using a luciferase reporter gene assay. The results showed that the mRNA expression levels of NEAT1 and SMAD3 were upregulated in the TGF‑β1‑treated HPAEpiC and BEAS‑2B cell lines, while the mRNA expression level of miR‑455‑3p was significantly decreased. In addition, silencing NEAT1 effectively alleviated the migratory ability, EMT and collagen generation of the epithelial cells. Following these experiments, NEAT1 was identified as a sponge for miR‑455‑3p, and SMAD3 was a target gene of miR‑455‑3p. NEAT1 downregulation or miR‑455‑3p mimic inhibited the migratory ability, EMT and collagen production of the epithelial cells; however, the effects were reversed by the overexpression of SMAD3. Furthermore, NEAT1 knockdown reduced the expression level of SMAD3 by increasing the expression level of miR‑455‑3p to further inhibit the migratory ability, EMT and collagen production of epithelial cells.

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