Long non-coding RNA NEAT1 participates in ventilator-induced lung injury by regulating miR-20b expression

Liu,Yi; Tang,Gang; Li,Jinyu

doi:10.3892/mmr.2022.12582

Long non-coding RNA NEAT1 participates in ventilator-induced lung injury by regulating miR-20b expression

Authors:
- Yi Liu
- Gang Tang
- Jinyu Li
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Affiliations: Department of Anesthesiology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 211100, P.R. China
Published online on: January 3, 2022 https://doi.org/10.3892/mmr.2022.12582
Article Number: 66
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding (lnc)RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to serve an important role in cancer, but its effects on ventilator‑induced lung injury (VILI) remain unclear. The present study aimed to investigate the role of lncRNA NEAT1 in alveolar macrophages (AMs) on ventilator‑induced lung injury (VILI). Mouse and cell models were established to detect NEAT1 expression, pathological changes in lung tissues, apoptosis of AMs, expression of the M1 phenotype marker, CD86 and M2 phenotype marker, CD206, and the expression levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor (TNF)‑α and inducible nitric oxide synthase (iNOS). The associations between NEAT1, microRNA (miRNA/miR)‑20b and STAT3 were predicted using StarBase and TargetScan, and verified via the dual‑luciferase reporter and RIP assays. NEAT1 short hairpin RNA and miR‑20b inhibitor were co‑transfected into AMs to assess the effect of NEAT1 and miR‑20b in VILI. The results demonstrated that NEAT1 was highly expressed in lung tissues of VILI mice and cell stretch (CS) treated AMs. Furthermore, NEAT1 knockdown inhibited lung injury and cell apoptosis induced by VILI. Compared with VILI mice or CS‑treated AMs, NEAT1 knockdown accelerated the phenotypic transformation from M1 to M2, and decreased the expression levels of IL‑1β, IL‑6, TNF‑α and iNOS. Notably, miR‑20b was identified as the target of NEAT1, and STAT3 was the target of miR‑20b. NEAT1 knockdown decreased STAT3 protein expression, the effects of which were reversed following transfection with miR‑20b inhibitor. Furthermore, the protective effect of NEAT1 knockdown on VILI was reversed following transfection with miR‑20b inhibitor. Taken together, the results of the present study suggest that NEAT1 knockdown promotes phenotypic transformation of AMs from M1 to M2 and alleviates lung injury and apoptosis of VILI by regulating miR‑20b expression.

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