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Published on: February 19, 2019
Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes
Thilde Nordmann Winther1, Kari Stougaard Jacobsen1, Aashiq Hussain Mirza2
1Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Kettegaard Allé 30, 2650 Hvidovre, Denmark ; Department of Paediatrics and Center for Non-Coding RNA in Technology and Health, Herlev Hospital, University of Copenhagen, Arkaden, 2730 Herlev, Denmark.
Insights
Hepatitis B e antigen positive children with chronic hepatitis B show altered microRNA levels in their plasma. These microRNAs may influence disease progression and liver damage in pediatric patients.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Hepatitis B e antigen positive (HBeAg-positive) children face significant risks of severe liver complications, including cirrhosis and hepatocellular carcinoma.
- Host immune responses to hepatitis B virus (HBV) infection in hepatocytes are implicated in liver damage.
- MicroRNAs are hypothesized to mediate the complex interplay between HBV and the host immune system.
Purpose of the Study:
- To identify microRNAs with abnormal plasma expression levels in HBeAg-positive children.
- To investigate microRNAs that target liver-specific genes, potentially influencing HBV pathogenesis.
Main Methods:
- Revisiting previous microRNA plasma screening data from HBeAg-positive, HBeAg-negative children with chronic hepatitis B (CHB), and healthy controls.
- Bioinformatics analysis to select microRNAs targeting liver-specific genes.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children.
Main Results:
- Thirteen microRNAs exhibited aberrant plasma expression in HBeAg-positive children and targeted liver-specific genes.
- Three specific microRNAs were found to be upregulated, while one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy controls.
- Plasma levels of these microRNAs were consistent between HBeAg-negative and healthy control groups.
Conclusions:
- The identified microRNAs may play a role in the progression of CHB in children.
- Further functional studies are necessary to fully understand the role of these microRNAs in the immunopathogenesis of childhood CHB.
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.
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