The Role Of Circular RNA In Early Allograft Dysfunction After Liver Transplantation

BackgroundEarly allograft dysfunction?EAD?following liver transplantation is associated with inferior prognosis of allograft and patient.In recent years,Circular RNA?circRNA?has emerged as an important component of endogenous RNA network.However,the expression profile of circRNA in EAD has not yet been elucidated.To improve the survival of patients and reducing the incidence rates of EAD,it is meaningful to explore the molecular mechanism of circular RNA in the development of EAD following liver transplantation.MethodsThe clinical data of recipients,donor and donor liver tissue in First affiliated hospital of Zhejiang university school of medicine between 2015 and 2017 were collected.The study compared circRNA sequencing of donor liver tissues between EAD patient and non-EAD patient to identify significant different circular RNAs between two groups.KEGG?Kyoto Encyclopedia of Genes and Genomes?and GO?Gene Ontology?analysis was applied to the different circular RNAs.Then different circular RNAs were further verified in liver tissue to explore the related circular RNA in the incidence of EAD following liver transplantation.We predict the targets of circular RNA to explore the mechanism of EADResultsA total of 431 circRNAs were identified differentially expressed between EAD donor liver tissue and non-EAD donor liver tissue,of which 332 circRNAs were significantly up-regulated and 99 circRNAs were down-regulated in EAD group.KEGG and GO analysis of differential circRNAs hosting genes reveal that top three pathway is Carbon metabolism,drug metabolism-cytochrome P450 and peroxisome.Hsa_circ₀048889 expression in EAD group were significantly lower than non-EAD group in the circular RNA sequencing data and were further verified in 43 donor liver tissue.The area under curve is 0.704 for hsa_circ₀048889 to predict the incidence of EAD.EAD and low expression of hsa_circ₀048889 are associated with poor prognosis.We construct a hsa_circ₀048889-miRNA-mRNA axis which involved the incidence of EAD.ConclusionsEAD is associated with poor prognosis in patients following LT.Hsa_circ₀048889 in donor liver tissue has predictive value for the incidence of EAD.