Sevoflurane regulating LncRNA Rik-203 contributes to neural differentiation via microRNA-466l-3p /BDNF pathway

Abstract Background: The anesthetics inhibit neural differentiation, induced neuron loss and cognitive impairment in young animals. However, the underlying mechanisms of anesthesia on neural differentiation and 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 Rik-203 was higher expressed in mice brain than other tissues and increased during neural differentiation. Sevoflurane decreased the level of Rik-203 in mice brain. Knockdown of Rik-203 repressed the neural differentiation derived from mouse embryonic stem cell with the downregulation of the neural progenitor cells markers Sox1 and Nestin. RNA pull-down showed that miR-466l-3p was highly bound to Rik-203 and mediated the function of Rik-203. Inhibition of miR-466l-3p restored the neural differentiation repressed by Rik-203 knockdown. BDNF was directly targeted by miR-466l-3p and also downregulated by sevoflurane. 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. Keywords: Anesthesia; sevoflurane; Rik-203; miR-466l-3p; BDNF; neural differentiation.