Related Experiment Video
Updated: Oct 18, 2025
Culturing and Manipulation of O9-1 Neural Crest Cells
Published on: October 9, 2018
Neuronal let-7b-5p acts through the Hippo-YAP pathway in neonatal encephalopathy
Vennila Ponnusamy1,2, Richard T H Ip3, Moumin A E K Mohamed3
1Ashford and St. Peter's Hospitals NHS Foundation Trust, Chertsey, UK.
Abstract:
Despite increasing knowledge on microRNAs, their role in the pathogenesis of neonatal encephalopathy remains to be elucidated. Herein, we identify let-7b-5p as a significant microRNA in neonates with moderate to severe encephalopathy from dried blood spots using next generation sequencing. Validation studies using Reverse Transcription and quantitative Polymerase Chain Reaction on 45 neonates showed that let-7b-5p expression was increased on day 1 in neonates with moderate to severe encephalopathy with unfavourable outcome when compared to those with mild encephalopathy. Mechanistic studies performed on glucose deprived cell cultures and the cerebral cortex of two animal models of perinatal brain injury, namely hypoxic-ischaemic and intrauterine inflammation models confirm that let-7b-5p is associated with the apoptotic Hippo pathway. Significant reduction in neuronal let-7b-5p expression corresponded with activated Hippo pathway, with increased neuronal/nuclear ratio of Yes Associated Protein (YAP) and increased neuronal cleaved caspase-3 expression in both animal models. Similar results were noted for let-7b-5p and YAP expression in glucose-deprived cell cultures. Reduced nuclear YAP with decreased intracellular let-7b-5p correlated with neuronal apoptosis in conditions of metabolic stress. This finding of the Hippo-YAP association with let-7b needs validation in larger cohorts to further our knowledge on let-7b-5p as a biomarker for neonatal encephalopathy.
Insights
Researchers identified microRNA let-7b-5p as a potential biomarker for neonatal encephalopathy. Increased let-7b-5p levels in newborns correlate with the severity of brain injury and apoptotic pathways, suggesting its role in pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neonatal encephalopathy (NE) is a serious condition with significant morbidity and mortality.
- The precise molecular mechanisms underlying NE pathogenesis are not fully understood.
- MicroRNAs (miRNAs) are emerging as critical regulators in various biological processes, including brain development and injury.
Purpose of the Study:
- To identify novel microRNAs involved in the pathogenesis of neonatal encephalopathy.
- To investigate the role of identified microRNAs in relation to the Hippo-YAP pathway and neuronal apoptosis.
- To explore the potential of microRNAs as biomarkers for predicting NE severity and outcome.
Main Methods:
- Next-generation sequencing of microRNAs from dried blood spots of neonates.
- Quantitative Polymerase Chain Reaction (qPCR) for validation in a cohort of 45 neonates.
- In vitro studies using glucose-deprived cell cultures.
- In vivo studies using animal models of hypoxic-ischaemic injury and intrauterine inflammation.
Main Results:
- let-7b-5p was identified as a significantly upregulated microRNA in neonates with moderate to severe NE.
- Increased let-7b-5p expression on day 1 correlated with unfavorable outcomes in NE patients.
- Mechanistic studies revealed that let-7b-5p is linked to the apoptotic Hippo-YAP pathway, influencing neuronal apoptosis via YAP and cleaved caspase-3 expression.
Conclusions:
- let-7b-5p is implicated in the pathogenesis of neonatal encephalopathy.
- The Hippo-YAP pathway is modulated by let-7b-5p, contributing to neuronal apoptosis under metabolic stress.
- let-7b-5p shows promise as a potential biomarker for neonatal encephalopathy, warranting further investigation in larger cohorts.
More Related Videos
07:36Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
