Circular RNA cZNF292 silence alleviates OGD/R-induced injury through up-regulation of miR-22 in rat neural stem cells (NSCs)

Abstract

Background: Hypoxic-ischaemic encephalopathy (HIE) is a prevailing severe brain damage disease in newborns, and caused by perinatal asphyxia cerebral ischaemia and reperfusion. Here, we investigated the role of cZNF292 in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neural stem cells (NSCs) injury, and explored the underlying molecular mechanism. Methods: Before NSCs were subjected to OGD/R treatment, NSCs were transfected with or without overexpressing cZNF292, si-cZNF292 or miR-22 inhibitor. Viability, apoptosis and potential molecular mechanism were examined. Cell viability and apoptotic rate were evaluated utilizing cell counting kit-8 (CCK-8) and flow cytometry. The cZNF292 and miR-22 expression was determined utilizing quantitative reverse transcription-PCR (qRT-PCR). Moreover, apoptosis and Wnt/b-catenin and PKC/ERK pathwaysassociated proteins were quantified applying western blot. Results: OGD/R repressed viability and promoted apoptosis of NSCs. Also, cZNF292 expression was promoted by OGD/R treatment. Moreover, cZNF292 overexpression further caused OGD/R-stimulated damage. Inversely, silencing cZNF292 alleviated OGD/R-stimulated damage in NSCs. In addition, miR-22 expression was negatively regulated by cZNF292. It was confirmed that silencing cZNF292 attenuated OGD/R-induced NSCs injury and promoted the activation of Wnt/b-catenin and PKC/ERK pathways via the up-regulation of miR-22. Conclusions: The cZNF292 silence alleviated OGD/R-induced injury through the up-regulation of miR-22 in NSCs, and which furnished the theoretical basis for further research on HIE progression.

Long Noncoding RNA/Circular RNA-miRNA-mRNA Axes in Ischemia-Reperfusion Injury

“…In addition, three circRNAs (cZNF292, TLK1, and circ_008018) were significantly increased in the MCAO/R mouse model and mouse neurons under OGD/R and knockdown of the circRNAs attenuated neuronal injury during cerebral I/R. These effects were related to cell apoptosis mediated by targeting miR-22/Wnt/b-catenin (under OGD/R), miR-335-3p/TIPARP (under OGD/R and cerebral I/R), and miR-99a/Pi3k/Akt/GSK3b (cerebral I/R) [ 116 – 118 ]. Furthermore, the expression levels of circTLK1 in patients with AIS were notably increased in comparison with healthy controls.…”

Circular RNAs in stem cells: from basic research to clinical implications

“…Recent findings revealed that many circRNAs contribute to the regulation of NSCs function. For example, Cao et al demonstrated that silencing circRNA cZNF292 alleviates oxygen-glucose deprivation/reperfusion (OGD/R)-induced NSC injury, thus promoting the activation of protein kinase C/extracellular signal-regulated kinase and Wnt/β-catenin pathways by upregulating miR-22 [115]. In another study, it was observed that during the differentiation of NSCs, the expression of circHIPK2 was decreased, which played a neu-Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20212510/926427/bsr-2021-2510.pdf by guest on 21 December 2021 roprotective role and facilitated nerve recovery after stroke.…”

A Narrative Review of Circular RNAs in Brain Development and Diseases of Preterm Infants

“…Through the neural stem cells experiment of oxygen-glucose deprivation/reperfusion (OGD/R)-induced injury, cZNF292 was over-expressed and then ORD/R injury exacerbated. Instead, cZNF292 had negative influence on miR-22, after which the insult was getting better by the way of wnt/β-catenin pathway ( Figure 2A ) ( 80 ). This signaling has been evidenced in importance for the differentiation of neurons and the formation of neural circuits, which are likely to be relevant to the arrangement of cerebrovascular and BBB ( 81 ).…”