Correlation analysis of circular RNAs involved in liver injury in mice with autoimmune hepatitis / 中国组织工程研究

ABSTRACT

BACKGROUND:The pathogenesis of autoimmune hepatitis has not been clearly elucidated.Circular RNA(CircRNA)is a research hotspot in the field of RNA and is involved in the pathogenesis of many autoimmune diseases.However,the role of CircRNA in autoimmune hepatitis remains unclear. OBJECTIVE:To investigate the relationship between CircRNA(CircRNA)and concanavalin A induced liver injury in mice with autoimmune hepatitis. METHODS:Bioinformatics analysis was performed on CircRNA profiles selected by previous microarray technology,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,so as to explore the potential biological functions of these differentially expressed genes.Twelve C57BL/6 mice were randomized into normal group and model group(n=6 per group).Autoimmune hepatitis model was established by tail vein injection of concanavalin A in the model group.Mice were killed at 12 hours after modeling to extract mouse liver and peripheral blood.The expression levels of CircRNAs were verified by qRT-PCR.Serum alanine aminotransferase and aspartate aminotransferase levels were detected by colorimetric method.The levels of oxidative stress indexes malondialdehyde and nitric oxide in mouse liver were detected by microplate method.The correlation between oxidative stress level and liver injury index was analyzed. RESULTS AND CONCLUSION:The results of GO analysis showed that the target genes with up-regulated CircRNAs expression were mainly involved in the biological processes of SNARE complex assembly regulation(P=0.004),their molecular functions were mainly metal ion binding(P=0.000 29),and the cell components were mainly enriched in CORVET complex(P=0.075).The biological processes involved in the down-regulated circRNAs target genes were mainly"negative regulation of pancreatic secretion"(P=0.000 42),the molecular functions were mainly"transcriptional activator activity"(P=0.025),and the cell components were mainly enriched in"extracellular components"(P=0.006).KEGG results showed that the target genes with up-regulated CircRNAs expression were mainly enriched in the"base excision-repair"signaling pathways(P=0.026).Compared with the normal group,serum alanine aminotransferase and aspartate aminotransferase levels and the levels of malondialdehyde and nitric oxide in mouse liver in the model group were significantly increased(P＜0.01).Compared with the normal group,the expression of two selected CircRNAs(mmu-circ-0001520 and mmu-circ-0001577)was increased in the model group(P＜0.05).Spearman correlation analysis showed that the expression of mmu-circ-0001520 and mmu-circ-0001577 was positively correlated with alanine aminotransferase,aspartate aminotransferase,malondialdehyde and nitric oxide.To conclude,the differential expression of CircRNAs is correlated with liver injury in autoimmune hepatitis mice.mmu-circ-0001520 and mmu-circ-0001577 are expected to be diagnostic biomarkers and therapeutic targets for autoimmune hepatitis.