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Altered Expression of Umbilical Cord Blood Levels of miR-181b and Its Downstream Target mUCH-L1 in Infants with Moderate and Severe Neonatal Hypoxic-Ischaemic Encephalopathy

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Abstract

Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neurological disability worldwide. No blood biomarker capable of early detection and classification of injury severity in HIE has been identified. This study aimed to investigate the potential of miRNA-181b (miR-181b) and its downstream target, ubiquitin C-terminal hydrolase-L1 (UCH-L1), to predict the severity of HIE. Full-term infants with perinatal asphyxia were recruited at birth and observed for the development of HIE, along with healthy controls. Levels of miR-181b and messenger UCH-L1 (mUCH-L1) in umbilical cord blood were determined using qRT-PCR. In total, 131 infants; 40 control, 50 perinatal asphyxia without HIE (PA) and 41 HIE, recruited across two separate cohorts (discovery and validation) were included in this study. Significant and consistent downregulation of miR-181b was observed in infants with moderate/severe HIE compared to all other groups in both cohorts: discovery 0.25 (0.16–0.32) vs 0.61 (0.26–1.39), p = 0.027 and validation 0.33 (0.15–1.78) vs 1.2 (0.071–2.09), p = 0.035. mUCH-L1 showed increased expression in infants with HIE in both cohorts. The expression ratio of miR-181b to mUCH-L1 was reduced in those infants with moderate/severe HIE in both cohorts: discovery cohort 0.23 (0.06–0.44) vs 1.59 (0.46–2.54), p = 0.01 and validation cohort 0.41 (0.10–0.81) vs 1.38 (0.59–2.56) in all other infants, p = 0.009. We have validated consistent patterns of altered expression in miR-181b/mUCH-L1 in moderate/severe neonatal HIE which may have the potential to guide therapeutic intervention in HIE.

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Funding

This research was funded by the National Children’s Research Centre, Crumlin (NCRC; B/14/1), the Health Research Board (HRB; CSA/2012/40), and a Science Foundation Research Centre Award (INFANT; 12/RC/2272).

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Authors and Affiliations

  1. Department of Paediatrics and Child Health, University College Cork, Cork, Ireland

    A. M. Looney, M. P. O’Sullivan, C. E. Ahearne, G. B. Boylan & Deirdre M. Murray

  2. INFANT Centre, University College Cork, Cork, Ireland

    A. M. Looney, M. P. O’Sullivan, C. E. Ahearne, G. B. Boylan & Deirdre M. Murray

  3. Pediatric Department, CLINTEC, Karolinska Institutet and Neonatal Department, Karolinska University Hospital, Stockholm, Sweden

    M. Finder & B. Hallberg

  4. Department of Pediatrics/Neonatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany

    U. Felderhoff-Mueser

Authors
  1. A. M. Looney
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  2. M. P. O’Sullivan
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  3. C. E. Ahearne
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  4. M. Finder
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  5. U. Felderhoff-Mueser
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  6. G. B. Boylan
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  7. B. Hallberg
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  8. Deirdre M. Murray
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Corresponding author

Correspondence to Deirdre M. Murray.

Electronic Supplementary Material

Supplementary figure 1

miR-181b expression in healthy controls (n = 18), infants with perinatal asphyxia (n = 23), mild HIE (n = 10), moderate HIE (n = 3) and severe HIE (n = 3). No significant changes in expression were observed between the controls, PA and HIE groups. (JPG 533 kb)

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Looney, A.M., O’Sullivan, M.P., Ahearne, C.E. et al. Altered Expression of Umbilical Cord Blood Levels of miR-181b and Its Downstream Target mUCH-L1 in Infants with Moderate and Severe Neonatal Hypoxic-Ischaemic Encephalopathy. Mol Neurobiol 56, 3657–3663 (2019). https://doi.org/10.1007/s12035-018-1321-4

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  • DOI: https://doi.org/10.1007/s12035-018-1321-4

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