Sevoflurane induces microRNA-18a to delay rat neurodevelopment via suppression of the RUNX1/Wnt/β-catenin axis

Abstract

Sevoflurane anesthesia is reported to repress neurogenesis of neural stem cells (NSCs), thereby affecting the brain development, but the underlying mechanism of sevoflurane on the proliferation of NSCs remains unclear. Thus, this study aims to discern the relationship between sevoflurane and NSC proliferation. Bioinformatics tools were employed to predict the expression of microRNA-18a (miR-18a) in 9-day-old neonatal rat hippocampal tissues after sevoflurane treatment and the downstream genes of miR-18a, followed by a series of assays to explore the relationship among miR-18a, runt related transcription factor 1 (RUNX1), and β-catenin in the hippocampal tissues. NSCs were isolated from the hippocampal tissues and subjected to gain-/loss-of-function assays to investigate the interactions among miR-18a, RUNX1, and β-catenin in NSCs and their roles in NSC development. Bioinformatics analysis and experimental results confirmed high expression of miR-18a in rat hippocampal tissues and NSCs after sevoflurane treatment. Next, we found that miR-18a downregulated RUNX1 expression, while RUNX1 promoted NSC proliferation by activating the Wnt/β-catenin signaling pathway. The behavioral experiments also showed that sevoflurane caused nerve injury in rats, whilst RUNX1 overexpression protected rat neurodevelopment. Our findings uncovered that sevoflurane attenuated NSC proliferation via the miR-18a-meidated RUNX1/Wnt/β-catenin pathway, thereby impairing rat neurodevelopment.

Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway

“…For example, TTYH3 inhibits apoptosis in CCA through the Wnt/β-catenin signaling pathway [ 30 ]. Furthermore, sevoflurane has been found to function in tumors via the Wnt/β-catenin signaling pathway [ 31 , 32 ]. Recent studies have shown that sevoflurane inhibits the proliferation and invasion of osteosarcoma cells by targeting the miR-203/Wnt/β-Catenin axis [ 33 ].…”

A Functional Single Nucleotide Polymorphism in the 3′ Untranslated Region of the Porcine JARID2 Gene Is Associated with Aggressive Behavior of Weaned Pigs after Mixing

“…MicroRNAs (miRNAs) regulate gene expression through translational repression, or mRNA deadenylation and mRNA decay [ 16 ]. There is growing evidence that miRNAs are associated with neurodevelopment and the development of various psychiatric diseases [ 17 , 18 ]. Overall levels of miRNAs in the prefrontal cortex have been reported to be down-regulated in patients with major depressive disorder following suicide compared to patients who died without psychiatric illness [ 19 ].…”

A Functional Single Nucleotide Polymorphism in the 3'-UTR of the Porcine JARID2 Gene is Associated with Aggressive Behavior of Weaned Pigs after Mixing

“…MicroRNAs (miRNAs) regulate gene expression through translational repression, or mRNA deadenylation and mRNA decay [16]. There is growing evidence that miR-NAs are associated with neurodevelopment and the development of various psychiatric diseases [17,18]. Overall levels of miRNAs in the prefrontal cortex have been reported to be down-regulated in patients with major depressive disorder following suicide compared to patients who died without psychiatric illness [19].…”