Characterization and functional prediction of the microRNAs differentially expressed in a mouse model of concanavalin A-induced autoimmune hepatitis

Abstract

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.

Circular RNAs associated with a mouse model of concanavalin A‐induced autoimmune hepatitis: preliminary screening and comprehensive functional analysis

“…Because more and more evidence has proved that circRNAs regulate the function of miRNAs acting as the ceRNAs [49–51], circRNA–miRNA coexpression networks were constructed to predict the relationships between DECs and the differentially expressed miRNAs in the same model [26]. Eight DECs and 43 target miRNAs were involved in the established circRNA–miRNA coexpression network (Fig.…”

“…From the established circRNA–miRNA and miRNA–mRNA interaction network in the same model [26], a latent circRNA–miRNA–mRNA network ‘ mmu_circ_0001520/mmu‐miR‐193b‐3p/MAPK10 ’ was constructed, and it was suggested that this predicted network was likely to be associated with the occurrence and development of AIH based on the literature research. Although no functional annotations of mmu_circ_0001520 have been presented, complement component 1, s subcomponent 1, the best transcript of this DEC, was annotated in the GO terms of ‘complement activation, lectin pathway’ (GO:0001867) in the BP category.…”

“…Based on the differently expressed miRNAs screened in the same model [26], the possible target miRNAs that might bind to the circRNA sequence were predicted by ‘miranda’ with the threshold set at ‘Total Score > 170’ and ‘Total Energy < −25’ [27]. The circRNA–miRNA networks were constructed by cytoscape software to illustrate the circRNA–miRNA interactions.…”

Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook

“…First, high-throughput detection techniques on screening the differentially expressed genes (involving the coding RNA and non-coding RNA) can be applied to this model, just like the research we are doing, to further explain the interaction between signal transduction pathways [ 61 , 89 , 90 ]. In particular, much more attention should be paid to the differentially expressed genes enriched in signaling pathways associated with T cell activation and NF-κB transcription.…”

Hepatoprotective Role of 4-Octyl Itaconate in Concanavalin A-Induced Autoimmune Hepatitis

“…Auto-immune hepatitis (AIH) is considered immune disorder-induced hepatic injury mediated by abnormal activation of immunocytes and production of proinflammatory mediators [11]. Concanavalin A-(Con A-) induced hepatitis has similar histopathological features and is widely used to establish AIH models in studies [12,13]. Con A can activate the Kupffer cells (KCs) and promote them to secrete proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), thus aggravating the inflammatory response and eventually causing hepatic damage [14,15].…”