LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3β-mediated neural differentiation.

The mechanism of anesthesia neurotoxicity remains largely to be determined. The effects of long noncoding RNAs (LncRNAs) on neural differentiation and the underlying mechanisms are unknown. We thus identified LncRNA Rik-203 (C130071C03Rik) and studied its role on neural differentiation and its interactions with anesthetic sevoflurane, miRNA and GSK-3β. We found that levels of Rik-203 were higher in hippocampus than other tissues and increased during neural differentiation. Sevoflurane decreased the levels of Rik-203. Rik-203 knockdown reduced mRNA levels of Sox1 and Nestin, the markers of neural progenitor cells, and decreased the count of Sox1 positive cells. RNA-RNA pull-down showed that miR-101a-3p was highly bound to Rik-203. Finally, sevoflurane, knockdown of Rik-203, and miR-101a-3p overexpression all decreased GSK-3β levels. These data suggest that Rik-203 facilitates neural differentiation by inhibiting miR-101a-3p's ability to reduce GSK-3β levels and that LncRNAs would serve as the mechanism of the anesthesia neurotoxicity.