Abstract
The mechanisms underlying severe liver injury after brain-dead (BD) donor liver transplantation (BDDLT) remain unclear. In this study, we aimed to explore the roles of lncRNAs and circRNAs in liver injury after BDDLT. Rat liver injury was detected in the sham, BD, control, and BDDLT groups. We examined the expression profiles of lncRNAs and circRNAs in the livers of the BDDLT and control group using microarray analysis. The main functions of the differentially expressed genes were analyzed by gene ontology (GO) and KEGG pathway enrichment analysis. In addition, we used bioinformatic analyses to construct related expression networks. Liver injury was aggravated in the BD and BDDLT groups. We found various mRNAs, lncRNAs, and circRNAs that were differentially expressed in the BDDLT group compared with those in the control group. Coding-noncoding gene co-expression (CNC) network analysis showed that expression of the lncRNA LOC102553657 was associated with that of the apoptosis-related genes including HMOX1 and ATF3. Furthermore, competing endogenous RNAs (ceRNAs) network analysis revealed that the lncRNA LOC103692832 and rno_circRNA_007609 were ceRNAs of rno-miR-135a-5p targeting Atf3, Per2, and Mras. These results suggest that lncRNAs and circRNAs play important roles in the pathogenesis and development of liver injury during BDDLT.
Highlights
In current practice, most liver gra s are obtained from braindead (BD) donors [1]
Correlation degree. ese mRNAs are involved in many biological processes such as the cell cycle, apoptosis, epithelialmesenchymal transition (EMT), and angiogenesis. e network revealed that the up-regulated long noncoding RNAs (lncRNAs) AABR06081886.1 was negatively correlated with Atf3, Hmox1, Angptl4, and Trib3, whereas the down-regulated lncRNA LOC100911923 was positively correlated with these four protein-coding genes, which are mainly involved in cell apoptosis (Figure 5)
We found that the expression levels of many lncRNAs were signi cantly associated with protein-encoding genes through correlation of expression levels. erefore, we established a Coding-noncoding gene co-expression (CNC) network to predict the relationship between lncRNAs and mRNAs. e network revealed that the up-regulated lncRNA AABR06081886.1 was negatively correlated with Atf3, Hmox1, Angptl4, and Trib3, whereas the down-regulated lncRNA LOC100911923 was positively correlated with these four protein-coding genes, which are mainly involved in cell apoptosis
Summary
Most liver gra s are obtained from braindead (BD) donors [1]. Brain death refers to the irreversible and permanent loss of all function throughout the entire brain, including the brainstem [2]. Previous clinical and experimental studies have shown that a series of complex pathophysiological changes occur during brain death, including hemodynamic instability, increased leukocyte in ltration, hormonal imbalance, induction of cytokines and chemokines, and increased expression of heat shock proteins. No precise biomarker has been identi ed which can predict liver injury following BD donor LT (BDDLT). Noncoding RNAs mainly include long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) [9]. LncRNAs are transcripts longer than 200 nucleotides which, because of their stability, are ideal biomarkers for disease research.
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