Identification of a Potential miRNA-mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF.

Abstract

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA–mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis.MethodsTranscriptome-wide microRNA (miRNA) and mRNA microarrays were used to define the miRNA and mRNA expression profiles of the PBMCs of HBV-ACLF patients in a discovery cohort. The targets of the miRNAs were predicted. We built a miRNA-mRNA regulatory network through bioinformatics analysis, and used quantitative real-time polymerase chain reaction (qRT-PCR) to assess the importance of candidate miRNAs and mRNAs. We also assessed the direct and transcriptional regulatory effects of miRNAs on target mRNAs using a dual-luciferase reporter assay.ResultsThe miRNA/mRNA PBMC expression profiles of the discovery cohort, of whom eight survived and eight died, revealed a prognostic interactive network involving 38 miRNAs and 313 mRNAs; this was constructed by identifying the target genes of the miRNAs. We validated the expression data in another cohort, of whom 43 survived and 35 died; miR-6840-3p, miR-6861-3p, JADE2, and NR3C2 were of particular interest. The levels of miR-6840-3p and miR-6861-3p were significantly increased in the PBMCs of the patients who died, and thus predicted prognosis (areas under the curve values = 0.665 and 0.700, respectively). The dual-luciferase reporter assay indicated that miR-6840-3p directly targeted JADE2.ConclusionWe identified a prognostic miRNA-mRNA co-regulatory network in the PBMCs of HBV-ACLF patients. miR-6840-3p-JADE2 is a potential miRNA–mRNA pair contributing to a poor prognosis.