lncRNA GMDS‑AS1 upregulates IL‑6, TNF‑α and IL‑1β, and induces apoptosis in human monocytic THP‑1 cells via miR‑96‑5p/caspase 2 signaling

Jiang,Lei; Li,Jinghui

doi:10.3892/mmr.2022.12583

lncRNA GMDS‑AS1 upregulates IL‑6, TNF‑α and IL‑1β, and induces apoptosis in human monocytic THP‑1 cells via miR‑96‑5p/caspase 2 signaling

Authors:
- Lei Jiang
- Jinghui Li
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Affiliations: Department of Emergency, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, P.R. China, Intensive Care Unit, Kunming Medical University Affiliated Yan'an Hospital, Kunming, Yunnan 650051, P.R. China
Published online on: January 3, 2022 https://doi.org/10.3892/mmr.2022.12583
Article Number: 67
Copyright: © Jiang 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 RNA (lncRNA) is considered a crucial modulator of the initiation and progression of several diseases. However, the roles of lncRNA in sepsis have yet to be fully elucidated. Thus, the aim of the present study was to investigate the effects of the lncRNA GDP‑mannose 4,6‑dehydratase antisense 1 (GMDS‑AS1) and its target in order to understand its role in the pathogenesis of sepsis. An in vitro sepsis model was established by lipopolysaccharide (LPS) induction. Reverse transcription‑quantitative PCR analysis was applied to detect the expression of inflammatory cytokines and the levels of GMDS‑AS1, microRNA (miR)‑96‑5p and caspase‑2 (CASP2). Flow cytometry was used to quantify the rate of apoptosis. In addition, the interaction between miR‑96‑5p and CASP2 was verified using a luciferase reporter assay. Western blot analysis was performed to assess the protein levels of CASP2 following alterations in GMDS‑AS1 and miR‑96‑5p expression using transfection. The levels of interleukin (IL)‑6, tumor necrosis factor‑α and IL‑1β were increased by LPS treatment in THP‑1 cells, whereas miR‑96‑5p expression was downregulated. miR‑96‑5p overexpression inhibited LPS‑induced inflammatory responses and apoptosis. In addition, GMDS‑AS1 expression increased, and upregulation of GMDS‑AS1 inhibited, the expression of miR‑96‑5p in the in vitro sepsis model. Moreover, CASP2 was confirmed to be a direct target of miR‑96‑5p. Therefore, the lncRNA GMDS‑AS1 regulated inflammatory responses and apoptosis by modulating CASP2 and sponging miR‑96‑5p in LPS‑induced THP‑1 cells. In summary, the findings of the present study demonstrated that lncRNA GMDS‑AS1 could promote the development of sepsis by targeting miR‑96‑5p/CASP2, indicating that the GMDS‑AS1/miR‑96‑5p/CASP2 axis may be a new therapeutic target and potential research direction for sepsis therapy.

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