Role of microRNA-124-3p/Bax axis in neonatal hypoxic-ischaemic encephalopathy

Abstract

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a neurological disease that can cause neonatal death. plays an important role in the development of various diseases. In this research, our aim was to investigate the potential function of miR-124-3p in regulating HIE and to find the underlying mechanism. Here, we discovered that miR-124-3p expression was reduced and cell apoptosis was increased in HIE rat model group. Interestingly, we identified that B cell lymphoma-2-associated X protein (Bax) was a direct target gene of miR-124-3p and Bax expression was negatively modulated by miR-124-3p in HIE. Functional experiments showed that miR-124-3p expression was reduced and Bax expression was increased in oxygen and glucose deprivation (OGD)-treated neurons. In addition, the cell viability of neurons was decreased and apoptosis was increased after OGD treatment. And miR-124-3p over-expression promoted cell viability and restrained apoptosis of the OGD-treated neurons. All these effects were reversed by Bax over-expression. Our results indicated that over-expression of miR-124-3p attenuated OGD-induced neuronal injury through targeting Bax, suggesting a potential role of miR-124-3p/Bax in the pathophysiology of HIE.

Cord blood microRNA-376c and microRNA-1268a as biomarkers for neonatal hypoxic-ischaemic encephalopathy: a diagnostic accuracy study

“…In an experimental animal study, Chen and colleagues 19 documented the potential role of miRNA-124-3p/Bax in the pathophysiology of HIE. In a study of miRNAs obtained from dried spots of blood, Ponnusamy et al 20 assessed the potential biomarkers for HIE in 30 newborn babies.…”

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

“…MiR-124 has been reported to regulate neurodevelopment [102], and upregulation of miR-124 expression level promotes microglial cells to switch from pro-inflammatory M1 type to anti-inflammatory M2 type [103,104]. In neonatal HIE rat model, miR-124-3p directly targets and regulates Bax, one of the pro-apoptotic members of the Bcl-2 family, and subsequently protects neurons from ischemic and hypoxic damage [105]. As previously described, antiinflammatory miR-124 was found in young microglia and might be able to indirectly affect the proliferation and gliosis of reactive astrocytes, playing a potential therapeutic role in immuneinflammatory neonatal brain injury.…”

“…Neonatal HIE [90]; Ischemic Stroke; miR-146a Negative regulators of astrocyte-mediated inflammatory responses Epilepsy [126]; ALS [127] miR-124 miR-124-3p Inhibition of astrocyte activation Neonatal HIE [105]; SCI [100] miR-155 miR-155-5p Promotion of astrocyte activation Neonatal HIE [97]; SCI [128] miR-136 miR-136-5p Promotion of astrocyte activation SCI [129] lncRNA H19 Promotion of astrocyte activation and proliferation I/R [113] lncRNA CRNDE Inhibition of astrocyte activation intrauterine infection-induced injury [117]; HIBD [130] circRNA HIPK2 Promotion of astrocyte activation by autophagy and ER stress TBI [131] circRNA_chr8 Promotion of astrocyte activation and neuroinflammation TBI [132] So far, we have exemplified and discussed ncRNAs involved in astrocytes activation and their possible or validated roles in neonates (Figure 1), They assist astrocytes in hypoxia, inflammatory cascades, cell proliferation, autophagy apoptosis, and differentiation fate. Of interest, some ncRNAs are highly conserved whereas the action of a subset of ncRNAs is age-dependent.…”