The regulatory role of microRNA-mRNA co-expression in hepatitis B virus-associated acute liver failure

Abstract

Introduction and objectives: Acute liver failure (ALF) is a dramatic disorder requiring intensive care. MicroRNAs (miRNAs) have been identified to play important roles in ALF. This study was performed to identify miRNA-mRNA co-expression network after ALF to investigate the molecule mechanism underlying the pathogenesis of ALF.

Materials and methods: The microarray dataset GSE62030 and GSE62029 were downloaded from Gene Expression Omnibus database. Overlapping differentially expressed miRNAs (DEmiRNAs) and genes (DEGs) were identified in liver tissues from patients with hepatitis B virus (HBV)-associated ALF in comparison with normal tissues from donors. Gene enrichment analysis was performed. Key pathways associated with the DEGs were identified. The miRNA-mRNA regulatory network was constructed.

Results: Total 42 DEmiRNAs and 523 DEGs were identified in liver tissues from patients with HBV-associated ALF. Gene ontology and pathways enrichment analysis showed upregulated DEGs were related to immune responses, inflammation, and infection, and downregulated DEGs were associated with amino acids, secondary metabolites and xenobiotics metabolism. In miRNA-mRNA co-expression network, DEGs were regulated by at least one DEmiRNA and transcription factor. Further analysis showed DEmiRNAs, including has-miR-55-5p, has-miR-193b-5p, has-miR-200b-3p, and has-miR-3175 were associated with amino acid metabolism, drug metabolism and detoxication, and signaling pathways including mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, Ras, and Rap1.

Conclusions: These miRNA-mRNA pairs and changed profiles were associated with and might be responsible for the impairment of detoxification and metabolism induced by HBV-associated ALF.

Keywords: Acute liver failure; Bioinformatics analysis; MicroRNA; Microarray.