Construction and function analysis of the LncRNA-miRNA-mRNA competing endogenous RNA network in autoimmune hepatitis

To construct the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on our microarray chip data for providing new insights into the pathogenesis of autoimmune hepatitis.

The ceRNA pairs were obtained by calculating the co-expression relationships among the differentially expressed lncRNAs (DELs), differentially expressed microRNAs (DEMis), and differentially expressed mRNAs (DEMs) with Pearson correlation analysis and hypergeometric distribution. The data of the differentially expressed genes were obtained from our previous studies in the concanavalin A-induced AIH mouse model. The biological functions of the ceRNA network were revealed by carrying out the GO and KEGG enrichment analysis. The expression of some differentially expressed genes constructed in the ceRNA pair was validated, and the correlation to liver injury was analyzed.

The mRNAs constructed in the ceRNA network were most significantly annotated in the GO terms of "inflammatory response" and enriched in "Cytokine-cytokine receptor interaction" and "MAPK signaling pathway". The differences in the expression of Gm38975, mmu-miR-125a-3p, and Map3k13 between the model group and control group were significant, and the expression of these genes at a transcriptional level was positively or negatively correlated to the activity of ALT and AST as well as the amount of MDA and NO.

Our work is the first in its kind to predict and illustrate the comprehensive lncRNA-miRNA-mRNA ceRNA network associated with the etiopathogenesis of AIH. This study indicates to lay the foundation for revealing the potential roles of ceRNAs in the occurrence of AIH and provide novel treatment targets for this disease.