lncRNA GAS5‑mediated miR‑23a‑3p promotes inflammation and cell apoptosis by targeting TLR4 in a cell model of sepsis

Gao,Zhenping; Huang,Dan

doi:10.3892/mmr.2021.12149

lncRNA GAS5‑mediated miR‑23a‑3p promotes inflammation and cell apoptosis by targeting TLR4 in a cell model of sepsis

Authors:
- Zhenping Gao
- Dan Huang
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Affiliations: Department of Critical Care Medicine, Taian Municipal Hospital, Tai'an, Shandong 271000, P.R. China, Department of Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
Published online on: May 11, 2021 https://doi.org/10.3892/mmr.2021.12149
Article Number: 510
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis is a syndrome characterized by organ dysfunction and an abnormal immune response to infection. A growing body of research has shown the importance of long non‑coding RNAs (lncRNAs) in tumorigenesis, virus replication, inflammatory injury and other pathological processes. The aim of the present study was to explore the role and potential mechanism of the lncRNA growth arrest‑specific 5 (GAS5) in the lipopolysaccharide (LPS)‑induced inflammation and apoptosis of THP‑1 cells. An in vitro sepsis model was established by treating THP‑1 cells with LPS. Apoptosis was detected by flow cytometry. The expression levels of IL‑6, IL‑1β and TNF‑α were detected using reverse transcription‑quantitative PCR (RT‑qPCR) and ELISA, and those of GAS5, microRNA (miR)‑23a‑3p and Toll‑like receptor 4 (TLR4) were detected by RT‑qPCR. The changes in the biological activity of THP‑1 cells induced by the silencing of GAS5 and overexpression of miR‑23a‑3p and TLR4 were investigated. The relationships among GAS5, miR‑23a‑3p and TLR4 were analyzed using luciferase reporter assays. The results revealed that LPS increased the expression of GAS5 in THP‑1 cells, and GAS5 knockdown effectively inhibited inflammation and cell apoptosis in the LPS‑induced sepsis model. In addition, the results of the luciferase reporter assays indicated that both GAS5 and TLR4 directly target miR‑23a‑3p. The expression of miR‑23a‑3p was downregulated whereas that of TLR4 was upregulated in the septic cells. Further experiments showed that the overexpression of TLR4 attenuated the suppressive effects of miR‑23a‑3p overexpression and GAS5 knockdown on LPS‑induced inflammation and apoptosis. In conclusion, the present study indicates that GAS5 strengthens LPS‑induced inflammation and apoptosis via the miR‑23a‑3p/TLR4 pathway.

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