Abstract
Hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and the mechanisms of its development and progression remain unclear. The aim of this study was to define the characteristics of peripheral blood mononuclear cell microRNAs in patients with HBV-ACLF. In this study, novel microRNA (miRNA) biomarkers of peripheral blood mononuclear cells (PBMCs) in patients with HBV-ACLF were characterised by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed 78 miRNAs were significantly differentially expressed in patients with HBV-ACLF compared to patients with chronic hepatitis B (CHB) and healthy controls. Among patients with HBV-ACLF, 17 dysregulated miRNAs increased or decreased more than 4-fold, of which eight miRNAs had higher expression levels than median level. qRT-PCR validation demonstrated that six miRNAs (hsa-miR-21-5p, hsa-miR-34c-5p, hsa-miR-143-3p, hsa-miR-143-5p, hsa-miR-374a-3p and hsa-miR-542-3p) may be useful as novel biomarkers for the diagnosis of HBV-ACLF. Five novel miRNAs (L-miR-1~5) were detected and two (L-miR-1 and L-miR-3) were significantly differentially expressed in patients with HBV-ACLF. Conclusions: The miRNA expression profile of PBMCs is altered in patients with HBV-ACLF, and a signature of six miRNAs may be a promising biomarker for HBV-ACLF progression.
Highlights
Hepatitis B virus (HBV) infection is a serious health issue throughout the world, in the Asia-Pacific region
Qualitative analysis of miRNAs using next-generation sequencing in peripheral blood mononuclear cells (PBMCs) from patients with HBV-ACLF or chronic hepatitis B and healthy controls
HBV infection is known to modulate the expression of host cellular miRNAs, which participate in the development of HBV-related liver diseases, though cellular miRNAs can regulate HBV gene transcription and replication[12]
Summary
Hepatitis B virus (HBV) infection is a serious health issue throughout the world, in the Asia-Pacific region. The establishment of sensitive and specific biomarkers for diagnosis and prediction of HBV-ACLF progression is critical for identifying patients who are high-risk. MicroRNAs (miRNAs), small endogenous non-coding regulatory RNA molecules with a length of approximately 22 nucleotides, participate in a variety of biological and pathological processes, including cell development and differentiation, apoptosis, stress and immune responses, and even carcinogenesis through the regulation of gene expression. Recent studies indicated that miRNAs might participate in the pathogenesis of liver injury[7,8] and initially showed the significance of the miRNA expression in peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients[9]. We hypothesised that the pathological process of HBV-ACLF would result in the alteration of the miRNA profile of PBMCs. In this study, we investigated the miRNA profile of PBMCs among patients with HBV-ACLF who met the criteria based on CLIF-SOFA scores[10]. Initial screening of dysregulated miRNAs was conducted using next-generation sequencing (NGS), and the selected dysregulated and novel potential miRNAs were confirmed by TaqMan probe-based quantitative real-time polymerase chain reaction (qRT-PCR)
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