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环状 RNA PARG 通过调节 miR-140-3p 影响脓毒症的进展。

Circular RNA PARG adjusts miR-140-3p to influence progression in sepsis.

机构信息

Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical College, Jiangxi, 341000, China.

Department of Emergency, Ganzhou People's Hospital &The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, 341000, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2023 May 31;69(5):105-111. doi: 10.14715/cmb/2023.69.5.17.

DOI:10.14715/cmb/2023.69.5.17
PMID:37571893
Abstract

Sepsis has been characterized as a frequent medical problem with high mortality and severe complication medical problem in the intensive care unit (ICU). Here, qRT-PCR was used to examine circRNA PARG expression levels in patients with sepsis and in human pulmonary microvascular endothelial cells (HPMEC). Lipopolysaccharide (LPS)-simulated HPMEC were hybridized using RNA-Fluorescence in situ hybridization to confirm the location of circRNA PARG and miR-140-3p. The biological role of downregulated circRNA PARGin cellular proliferation, apoptosis, and inflammatory and apoptosis responses was evaluated. performed A dual-luciferase reporter assay was performed to determine the relationship between the circRNA PARG with miR-140-3p. In this study,circRNA PARG aberrant expression was found, and the effects of circRNA PARG on lipopolysaccharide (LPS)-stimulated apoptosis of HPMEC cells were further investigated. Down-regulated circRNA PARG led to significant alleviation of LPS-simulated cell apoptosis via inhibition of inflammatory and apoptosis-related genes, while upregulated circRNA PARG exhibited the opposite effects. Further findings indicated that circRNA PARG positively modulated the relative level of miR-140-3p, which has been confirmed using the luciferase reporter assay. Upregulated circRNA PARG led to a reversal of LPS-simulated cells after transfection of miR-140-3p mimic. In general, a novel insight into understanding the important effects of circRNA PARG in sepsis is provided.

摘要

脓毒症是重症监护病房(ICU)中常见的高死亡率和严重并发症的医学问题。在这里,使用 qRT-PCR 检查了脓毒症患者和人肺微血管内皮细胞(HPMEC)中 circRNA PARG 的表达水平。使用 RNA-荧光原位杂交将 LPS 模拟的 HPMEC 杂交,以确认 circRNA PARG 和 miR-140-3p 的位置。评估了下调 circRNA PARG 在细胞增殖、凋亡、炎症和凋亡反应中的生物学作用。进行了双荧光素酶报告基因测定,以确定 circRNA PARG 与 miR-140-3p 之间的关系。在这项研究中,发现 circRNA PARG 表达异常,并进一步研究了 circRNA PARG 对 LPS 刺激的 HPMEC 细胞凋亡的影响。下调 circRNA PARG 通过抑制炎症和凋亡相关基因导致 LPS 模拟的细胞凋亡显著减轻,而上调 circRNA PARG 则表现出相反的效果。进一步的研究结果表明,circRNA PARG 正向调节 miR-140-3p 的相对水平,这已通过荧光素酶报告基因测定得到证实。转染 miR-140-3p 模拟物后,上调的 circRNA PARG 导致 LPS 模拟的细胞逆转。总之,提供了对脓毒症中 circRNA PARG 重要作用的新认识。

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