LncRNA Rik-203 Contributes to Sevoflurane Induced Neurotoxicity?

Abstract

Background: The anesthetics inhibit neural differentiation, induce neuron loss and cognitive impairment in young animals. However, the underlying mechanisms of anesthesia on neural differentiation are unknown. Methods: Embryonic stem cells (ESCs) and mice received sevoflurane anesthesia. RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-203. The binding of miRNA with mRNA of BDNF was presented by the luciferase assay. Results: Here we found that LncRNA Riken-203(Rik-203) was highly expressed in mice brain and was upregulated during neural differentiation. Sevoflurane decreased the amount of Rik-203 in mice brain. Knockdown of Rik-203 repressed the neural differentiation derived from mouse embryonic stem cell and downregulated the neural progenitor cells markers Sox1 and Nestin. RNA pull-down showed that miR-466l-3p was highly bound to Rik-203. Inhibition of miR-466l-3p restored the neural differentiation repressed by Rik-203 knockdown. Brain derived neurotrophic factor (BDNF), which was downregulated by sevoflurane, was also directly targeted by miR-466l-3p. Overexpression of BDNF restored the neural differentiation repressed by miR-466l-3p and Rik-203 knockdown. Conclusion: Our study suggested that sevoflurane related LncRNARik-203 facilitates neural differentiation by inhibiting miR-466l-3p's ability to reduce BDNF levels.

Effects of lncRNA HOXA11-AS on Sevoflurane-Induced Neuronal Apoptosis and Inflammatory Responses by Regulating miR-98-5p/EphA4

“…As is well known, lncRNAs are related to many biological processes during development (such as neuronal development, plasticity, disease, and evolution) and are related with sevoflurane [ 19 , 20 ]. For example, overexpression of Gm15621 [ 21 ] or knockdown of Gm43050 [ 22 ] both attenuates sevoflurane-induced neuronal apoptosis and inflammatory responses.…”

Knockdown of lncRNA NKILA suppresses sevoflurane-induced neuronal cell injury partially by targeting miR-205-5p/ELAVL1 axis

“…With its analgesic and anesthetic effect, Sev also has roles in neuronal injury and oncogenesis (Lu et al 2020;. In Sev promotion or suppression of neuronal dysfunction, non-coding RNAs, including lncRNAs and miRNAs are differently expressed, and the dysregulation of these RNAs can alter downstream functional genes in neural progenitor cells (Zhang et al 2019(Zhang et al , 2020a and hippocampal neurons (Chen et al 2016;Wang JY et al 2018;).…”

“…Several years ago, a microarray study revealed that long non-coding RNAs (lncRNAs) together with their messenger RNAs (mRNAs) targets were abnormally expressed in Sev-induced hippocampal neuronal apoptosis (Chen et al 2016). Since then, many studies have shown that lncRNAs are involved in Sev-induced neurontoxicity via serving as naturally competing endogenous RNAs (ceRNAs), such as Rik-203/microRNA (miRNA)-466l-3p/brain-derived neurotrophic factor (Zhang et al 2020a). LncRNAs are a group of >200 bp RNAs and show specific spatiotemporal expression profiles.…”

Up-regulation of miR-20a ameliorates sevoflurane anesthesia-induced cognitive impairment in rats by targeting EphA4

“…MicroRNAs (miRNAs) are a class of small noncoding RNAs that can bind to the 3'-untranslated region (3'-UTR) of the transcript of their homologous target genes, thereby regulating their expression [9]. Extensive studies have confirmed a broad association between miRNAs and anesthesia-related cognitive impairment [9][10][11]; miRNAs, such as miR-665, miR-572, and miR-181, have been reported to affect POCD progression, suggesting that these miRNAs could serve as promising therapeutic targets for treating POCD [12].…”