Comprehensive Analysis of the Differentially Expressed Transcriptome with ceRNA Networks in a Mouse Model of Liver Cirrhosis

Abstract

Background: Hepatic cirrhosis is the consequence of various chronic liver disease for which there is no curative treatment. In this study, based on RNA sequencing (RNA-seq) and subsequent bioinformatic analysis, we aim to explore the biological function of non-coding RNAs (ncRNAs) in hepatic cirrhosis. Methods: The hepatic cirrhosis models were induced by the intraperitoneal injection of carbon tetrachloride (CCl4). The transcriptome profile was aquired by RNA-seq, of which result was verified by quantitative real-time PCR (qRT-PCR). The competing endogenous RNA (ceRNA) networks were visualized by Cytoscape software. The enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted. Results: The differentially expressed transcript of liver cirrhosis is consist of 2369 mRNAs, 374 lncRNAs, 91 circRNAs and 242 miRNAs (|log2(fold change)|≥1 and P<0.05). The RNA-seq results were highly consistent with qRT-PCR validation of DEGs (four upregulated and four down-regulated, including ENSMUSG00000047517, ENSMUST00000217449, novel-circ-001366, miR-383-5p, ENSMUSG00000078683, ENSMUST00000148206, novel-circ-002669 and miR-216a-5p). Based on ceRNA theory, a circRNA-lncRNA co-regulated ceRNA network was established. Enrichment analysis revealed the potential key regulatory process during the liver cirrhosis progression. Conclusion: In conclusion, the present study comprehensively analyzed differentially expressed transcripts in CCl4-induced liver cirrhosis. Our findings explored the gene signatures for liver cirrhosis’ diagnosis and precise treatment.