Circulating microRNAs in preterm white matter injury: a systems biology/qPCR-based pilot study

Area of Science:

• Neonatal neurology
• Molecular diagnostics
• Biomarker discovery

Background:

• White matter injury (WMI) in preterm infants (PTIs) leads to neurodevelopmental issues, with a need for early molecular biomarkers.
• Neonatal biosample limitations hinder high-throughput methods like next-generation sequencing (NGS) for biomarker discovery.
• Quantitative PCR (qPCR) is explored as a primary discovery tool for circulating miRNA biomarkers of WMI.

Purpose of the Study:

• To evaluate the feasibility of qPCR as a primary discovery tool for circulating miRNA biomarkers of WMI in PTIs.
• To support qPCR findings with systems biology modeling and selective NGS validation.
• To identify specific miRNAs and their regulatory roles in WMI pathogenesis.

Main Methods:

• Plasma miRNAs from PTIs with and without WMI were profiled using qPCR after hemolysis screening.
• Candidate miRNAs were identified using brain-specific regulatory networks.
• ROC analysis, gene ontology, and Boolean logic modeling were employed for diagnostic and functional assessment.

Main Results:

• miR-23a-3p and miR-17-5p showed differential expression and moderate diagnostic power (AUCs 0.71, 0.68).
• Oligodendrocyte-specific miRNAs were consistently low.
• Boolean simulations linked miR-23a and miR-17 to oligodendrocyte maturation via PTEN/PI3K/Akt pathways, aligning with qPCR data.

Conclusions:

• qPCR coupled with systems biology modeling is a viable and sensitive approach for discovering miRNA biomarkers in clinically constrained neonatal populations.
• This study challenges the default reliance on NGS for biomarker discovery, repositioning qPCR as a powerful primary tool.
• The integrated approach provides mechanistic insights into WMI pathogenesis by linking specific miRNAs to oligodendrocyte maturation pathways.