Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

• Published in: Innate immunity (London, England) Vol. 26; no. 2; pp. 152 - 161
• Main Authors: Wang, Yijun, Xu, Ziqiang, Yue, Dongyou, Zeng, Zhenhua, Yuan, Weijie, Xu, Ke
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2020; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Adolescent; Adult; Aged; Cell Line; Cytokines - blood; Cytokines - genetics; Down-Regulation; Female; Humans; IL-1β; Inflammation; Inflammation - blood; Inflammation - genetics; Inflammation - metabolism; Interleukin 6; Interleukin-1beta - blood; Interleukin-1beta - genetics; Interleukin-6 - genetics; Interleukin-6 - metabolism; Life span; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Male; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; NF-kappa B - blood; NF-kappa B - genetics; NF-κB protein; Original; Peripheral blood; Prognosis; Reporter gene; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; RNA, Small Interfering; Sepsis; Sepsis - blood; Sepsis - genetics; Sepsis - physiopathology; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Up-Regulation; Sepsis; LncRNA CRNDE; miR-181a-5p; inflammation; TLR4
• ISSN: 1753-4259; 1753-4267; 1753-4267
• DOI: 10.1177/1753425919880946

This investigation was performed to verify whether lncRNA CRNDE sponging miR-181a-5p was involved with sepsis-relevant inflammatory dysfunctions. Aggregately 136 sepsis patients and 151 healthy people were recruited, and their fasting peripheral blood was gathered to detect expressions of CRNDE and miR-181a-5p. In addition, THP-1 cells were transfected with si-CRNDE, miR-181a-5p mimic, pcDNA3.1-TLR4 and si-TLR4, and then sepsis-specific inflammatory cytokines within the cells were quantified. The sponging relationships between CRNDE and miR-181a-5p, as well as between miR-181a-5p and TLR4, were ascertained by means of luciferase reporter gene assay. The experimental results revealed that over-expressed CRNDE and under-expressed miR-181a-5p were associated with shortened lifespan of sepsis patients. Mechanically, si-CRNDE-1 and miR-181a-5p mimic were able to reverse the promoting effects of LPS on production of NF-kB, TNF-α, IL-1β and IL-6 by THP-1 cells. Moreover, the expressional change of miR-181a-5p in THP-1 cells was in part owing to its being sponged by CRNDE. Lastly, TLR4, subjected to targeted modification of miR-181a-5p, was capable of disturbing the contribution of CRNDE and miR-181a-5p to THP-1 cells’ release of NF-kB, TNF-α, IL-1β and IL-6. Collectively, the CRNDE/miR-181a-5p/TLR4 axis seemed to have potential in modifying sepsis-related inflammatory pathogenesis, which offered a direction for sepsis diagnosis and treatment.