1. College of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, 030619, PR China.
2. Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, PR China.
#Co-senior authors with equal contributions to this work.
In order to investigate the altered expression of microRNAs (miRNAs) in the development of autoimmune hepatitis (AIH), the aberrantly expressed miRNAs in the concanavalin A (Con A)-induced AIH mouse model were identified for the first time with microarray in this study. A total of 49 miRNAs (31 up- and 18 down-regulated) were screened out, and the qRT-PCR validation results of 12 chosen miRNAs were consistent with the microarray data. Combined with the profiling of differently expressed mRNAs in the same model (data not shown), 959 predicted target genes (601 for up- and 358 for down-regulated miRNAs) were obtained according to the intersection of databases miRWalk and miRDB, and several hub genes were obtained from the regulatory networks, including Cadm1 and Mier3. These target genes were significantly enriched in the Gene ontology (GO) terms of “transcription, DNA-templated”, and were annotated in 47 signaling pathways, comprising “Wnt signaling pathway”, “Hippo signaling pathway”, “Ferroptosis” and “mitogen-activated protein kinase (MAPK) signaling pathway”, according to the GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the miRNA-GO-network, mmu-miR-193b-3p were exhibited in 33 GO terms of biological processes (BP), and the most significantly regulated GO term in BP categories was “regulation of transcription, DNA-templated”. While in the miRNA-pathway-network, mmu-miR-7005-5p were enriched in 37 pathways, which was more than the other specifically expressed miRNAs, and the most significantly enriched pathways were “Endocytosis” and “MAPK signaling pathway”. In conclusion, these differently expressed miRNAs seemed to be associated with the onset of AIH, and have the potential to serve as the new targets on the treatment of this disease.
Keywords: autoimmune hepatitis, concanavalin A, microRNA, microarray, Gene Ontology, KEGG