Down-regulation of long non-coding RNA XIST aggravates sepsis-induced lung injury by regulating miR-16-5p

Abstract

This study aims to explain the role and related mechanisms of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in sepsis-induced acute lung injury (ALI). The in vivo septic models and in vitro septic model were established. In animal models, the lung injury of the rats was evaluated after XIST was overexpressed. In cell models, the effects of XIST and microRNA (miR)-16-5p on ALI was detected by MTT assay, Western blot and ELISA. The interaction between XIST and miR-16-5p was investigated by bioinformatics analysis, dual-luciferase reporter assay, RIP assay and RNA pull-down assay. We found that XIST expression was down-regulated in lung tissues of septic rats and lipopolysaccharide-stimulated cells, while the expression of miR-16-5p was up-regulated. Down-regulation of XIST significantly promoted pulmonary edema, increased the levels of TNF-α, IL-1β and malondialdehyde, inhibited the cell viability and decreased the level of superoxide dismutase. Mechanistically, it was confirmed that XIST could sponge miR-16-5p, and thus repress its expression, and the transfection of miR-16-5p mimics could reverse the effects of XIST over-expression in the cell model. Collectively, it is concluded that XIST reduces sepsis-induced ALI via regulating miR-16-5p.

Identification and validation of oxidative stress-related genes in sepsis-induced myopathy

“…[ 40 ] Another investigation provided evidence that the long non-coding RNA X inactive specific transcript has the potential to mitigate sepsis-induced acute lung damage by targeting miR-16-5p. [ 41 ] Furthermore, research has shown that the overexpression of miR-16-5p effectively inhibits the inflammatory response via the repression of PIK3R1-mediated activation of the PI3K/Akt/NF-κB pathway to exerting anti-inflammatory effect. [ 42 ] All of these data suggest the importance of miR-16-5p in oxidative stress and inflammatory response.…”

Exosomal Circvma21 Derived From Adipose-Derived Stem Cells Alleviates Sepsis-Induced Acute Kidney Injury by Targeting Mir-16-5p

“…MiR-16-5p has been confirmed to play a vital role in sepsis-related diseases (28,29). Song et al revealed that miR-16-5p promoted sepsis-induce lung injury, which enhanced the apoptosis, inflammation, and oxidative stress of LPS-induced airway epithelial cells (30). Importantly, our previous research showed that miR-16-5p was upregulated in septic patients and LPS-treated cells, which might aggravate sepsis process via promoting aerobic glycolysis (31).…”

Long Non-Coding RNAs as Biomarkers and Therapeutic Targets in Sepsis

“…TUG1 could also alleviate pulmonary inflammation and lung vascular endothelial cell injury (89). X inactive specific transcript (XIST) was observed to be overexpressed in a lung injury rat model, and the researchers concluded that XIST might ameliorate sepsis-induced lung injury by modulating miR-16-5p (91). Hence, lncRNAs play important roles in sepsis-induced lung injury and they may become new diagnostic and therapeutic biomarkers for lung injury caused by sepsis (Figure 3).…”