Neuronal let-7b-5p acts through the Hippo-YAP pathway in neonatal encephalopathy
View/ Open
Volume
4
Publisher
Publisher URL
DOI
10.1038/s42003-021-02672-3
Journal
COMMUNICATIONS BIOLOGY
Issue
Metadata
Show full item recordAbstract
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-7b5p is associated with the apoptotic Hippo pathway. Significant reduction in neuronal let-7b5p 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.