Long noncoding RNA colorectal neoplasia differentially expressed alleviates sepsis‐induced liver injury via regulating miR‐126‐5p

Abstract

In this study, we intended to determine the detailed function and mechanism of long noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in liver injury induced by sepsis. Cecal ligation and perforation (CLP) models were adopted to induce sepsis in vivo with rats, and hepatic epithelial cells L02 were treated with lipopolysaccharide (LPS) to mimic sepsis in vitro. Enzyme‐linked immunosorbent assay was conducted to detect the levels of tumor necrosis factor (TNF‐α), interleukin‐6 (IL‐6), interleukin‐10 (IL‐10), and interferon‐γ (IFN‐γ) in the serum of rats. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to measure the expressions of CRNDE and microRNA‐126‐5p (miR‐126‐5p). Flow cytometry analysis and Cell Counting Kit‐8 (CCK‐8) method were carried out followed by the up‐ or downregulation of CRNDE and miR‐126‐5p to monitor the proliferation and apoptosis of L02 cells, respectively. Western blot was then applied to determine the expressions of cysteinyl aspartate specific proteinase 3 (caspase 3), poly(ADP‐ribose)polymerase (PARP), cytochrome c, and BCL2‐like 2 (BCL2L2). The interactions between CRNDE with miR‐126‐5p and miR‐126‐5p with BCL2L2 were determined through bioinformatics, qRT‐PCR, dual luciferase reporter assay, and RNA immunoprecipitation assay. CRNDE was significantly decreased in liver tissues and hepatic cells in sepsis models. Upregulation of CRNDE promoted the viability of L02 cells and inhibited their apoptosis, while downregulation of CRNDE had opposite effects. The expression of CRNDE in liver tissues of septic rats was correlated with the expression miR‐126‐5p. It was also demonstrated that the transfection of miR‐126‐5p mimics reversed the inhibitory effect induced by CRNDE on apoptosis of L02 cells. CRNDE could specifically bind to miR‐126‐5p and reduce its expression, in turn promote the expression of BCL2L2. Additionally, CRNDE overexpression in rats ameliorated liver injury induced by sepsis. Downregulated CRNDE aggravates hepatic injury via regulating miR‐126‐5p and BCL2L2 during sepsis.

Influences of Regulation of miR-126 on Inflammation,Th17/Treg Subpopulation Differentiation, and Lymphocyte Apoptosis through Caspase Signaling Pathway in Sepsis

“…In our study, it also showed that the proportion of Th17 and Treg subsets changed significantly in sepsis and the differentiation of Th17 and Treg subsets could be regulated by the expression level of miR-126 in lymphocytes of septic rats. A study on septic rats has shown that upregulation of miR-126 by transfection could heighten the apoptosis of liver epithelial cells, which proved that miR-126 could improve liver injury in sepsis [35]. Another study on burn tissues and endothelial cells has shown that the upregulation of miR-126 could inhibit the apoptosis of endothelial cells [36].…”

Long non-coding RNA CASC7 Contributes to the Progression of Sepsis-Induced Liver Injury by Targeting miR-217/TLR4 Axis

“…It has been well-identi ed that multiple lncRNAs are involved in the development of sepsis-induced liver injury. For example, lncRNA colorectal neoplasia, differentially displayed, relieves sepsis-caused liver damage by targeting miR-126-5p [28]. Circulating lncRNA NEAT1 is correlated with an unfavorable prognosis, high severity, and increased risk in sepsis patients [29].…”

Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

“…Functional studies in LPS-induced macrophages showed that lncRNA NEAT1 interacted with Let-7a, targeting TLR4 that in turn contributed to the LPS-induced inflammatory response ( Zhang and Niu, 2019 ). Another lncRNA, which functions via ceRNA mechanism, lncRNA CRNDE overexpression in rats ameliorated sepsis-induced liver injury by inhibiting hepatic epithelial cell apoptosis through binding to miR-126-5p, and in turn promoting the expression of BCL2L2 ( Li et al., 2020 ).…”