Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

Abstract

Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children. Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels. Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs' role in the immunopathogenesis of childhood CHB.

MicroRNA Sequencing Identifies a Serum MicroRNA Panel, Which Combined With Aspartate Aminotransferase to Platelet Ratio Index Can Detect and Monitor Liver Disease in Pediatric Cystic Fibrosis

“…There is supporting evidence that hepatic stellate cells (HSCs) and macrophages can influence the differentiation of liver progenitor cells into reactive biliary cells and bile ducts by the Notch pathway, therefore suggesting a potential role of miR‐34a in the manifestation of CFLD. A potential role of miR‐365 has been implicated in pediatric CLD, including biliary atresia, and increased levels of circulating miR‐365a‐3p have been found in the plasma of children with hepatitis B, suggesting its potential as a biomarker for disease progression . However, further mechanistic studies are required to fully elucidate the role of miR‐34a‐5p and miR‐365a‐3p in the pathogenesis of these pediatric liver diseases.…”

“…A potential role of miR-365 has been implicated in pediatric CLD, including biliary atresia, (44) and increased levels of circulating miR-365a-3p have been found in the plasma of children with hepatitis B, suggesting its potential as a biomarker for disease progression. (33,45) However, further mechanistic studies are required to fully elucidate the role of miR-34a-5p and miR-365a-3p in the pathogenesis of these pediatric liver diseases.…”

Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease

“…In a more recent study, Winther et al identified liver specific target genes in plasma of HBeAg+ children (Table 3) [149]. Using the raw data from the original study [147], plasma miRNA expression was re-analyzed from HBeAg+, HBeAg− and the healthy control groups.…”

Identification of valid reference genes for microRNA expression studies in a hepatitis B virus replicating liver cell line

“…Current knowledge on the pathogenesis at the molecular level is, however, limited [ 13 ]. We previously identified a panel of differentially expressed microRNAs in plasma from children with CHB [ 14 ] and furthermore showed that a number of the identified microRNAs had liver-specific target genes [ 15 ]. Liver tissue samples are unavailable as the majority of children with CHB are asymptomatic.…”