Circ_0001498 contributes to lipopolysaccharide-induced lung cell apoptosis and inflammation in sepsis-related acute lung injury via upregulating SOX6 by interacting with miR-574-5p

Abstract

Circular RNAs (circRNAs) have important regulation in in sepsis-related acute lung injury (ALI). Circ_0001498 was significantly overexpressed in sepsis-induced acute respiratory distress syndrome. The aims of this study were to explore role and mechanism of circ_0001498 in lipopolysaccharide (LPS)-treated WI-38 cells. Human samples were collected from 56 sepsis patients and 46 healthy volunteers at Liyang People's Hospital. Circ_0001498, microRNA-574-5p (miR-574-5p) or sex-determining region Y-related high-mobility-group box 6 (SOX6) levels were detected via reverse transcription-quantitative polymerase chain reaction assay. Cell viability was determined through Cell Counting Kit-8 assay. Apoptosis rate was examined by flow cytometry. Western blot was used for measurement of proteins. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Target relation was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001498 was overexpressed in sepsisrelated ALI patients and LPS-treated WI-38 cells. Silencing circ_0001498 reduced LPS-induced cell apoptosis and inflammation. Circ_0001498 interacted with miR-574-5p. The regulation of circ_0001498 knockdown was abolished by miR-574-5p inhibitor. Furthermore, miR-574-5p directly targeted SOX6 and circ_0001498 upregulated SOX6 via targeting miR-574-5p. Overexpression of miR-574-5p alleviated LPS-induced cell injury by downregulating SOX6. This research identified that circ_0001498 facilitated sepsis-related ALI progression by targeting miR-574-5p to upregulate SOX6.

LncRNA HOTTIP as a diagnostic biomarker for acute respiratory distress syndrome in patients with sepsis and to predict the short-term clinical outcome: a case-control study

“…It was identified as sepsis-associated miRNA, and downregulation of its levels can predict the development of acute kidney injury in patients with sepsis [ 35 ]. MiR-574-5p was significantly reduced in acute lung injury associated with sepsis [ 36 ] and was recognized as a miRNA associated with death in patients with sepsis [ 37 ]. Consistent with previous studies, we also found that miR-574-5p levels were generally lower in patients with sepsis.…”

Changes in miRNA expression in the lungs of pigs supplemented with different levels and forms of vitamin D

“…However, the in-silico study we performed showed that miR-574 is not significantly associated with any of the four cancer-related pathways. Therefore, the results of a recent study by Wei et al seem to be more interesting [ 37 ]. These researchers discovered a mechanism of circ_0001498 action that stimulates sepsis-induced acute lung failure syndrome.…”

“…Wei et al found that overexpression of circ_0001498 mediated by miR-574 upregulates SOX6 . In contrast, overexpression of miR-574 had the opposite effect (downregulation of SOX6 ), resulting in attenuation of cell damage [ 37 ]. The effect of the increased miR-574 expression on attenuating sepsis-induced lung injury was also confirmed in another study [ 38 ].…”

Sepsis-Induced Acute Lung Injury Is Alleviated by Small Molecules from Dietary Plants via Pyroptosis Modulation

“…A range of types of programmed cell death has been confirmed to play a pivotal role in the development of sepsis-induced ARDS; the representative ones include circ_0001498/miR-574-5p/SOX6 axis-involved apoptosis, bleb formation to epithelial cells necrosis, Sirtuin 6-regulated alveolar macrophages autophagy, Mucin 1/keap-1-involved ferroptosis, and Gasdermin D (GSDMD)-dominant pyroptosis, among which pyroptosis has been received most in-depth investigation. Pyroptotic cell death is a double-edged sword since it released pro-inflammatory mediators to gather the nearby immune cells around the pathogenic infected sites and subsequently destroy their replication niches and enhance adaptive immune responses.…”