Sevoflurane-mediated LncRNA Rik-201 And Rik-203 Modulates Neural Development By Regulating The Sox6 Through Sequestering MiRNAs

Objective: sevoflurane-mediated Long non-coding RNAs(LncRNAs)play important roles in epigenetic regulatory function during the development processes.In this study we found that through alternative splicing,LncRNA C130071C03 Rikenvariants Rik-201 and Rik-203 are both expressed highly in brain,and increase gradually during neural differentiation,However,the function of Rik-201 and Rik-203 is unknown.Materials and Methods: Embryonic stem cells(ESCs);RNA sequencing;gene expression of m RNAs,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-201 and Rik-203.The binding of miRNA with m RNA of Sox6 was presented by the luciferase assay.Results: Rik-201 and Rik-203 promote neural differentiation from mouse embryonic stem cells treated with sevoflurane.Moreover,Rik-201 and Rik-203 functioned as the competing endogenous RNA(ce RNA)to repress the function of miR-96 and miR-467a-3p respectively and modulate the expression of Sox6 to further regulate neural differentiation.Knockout of the Rik-203 and Rik-201 induced high ratio of brain developmental retardation.Further we found that C/EBPβmight potentially activated the transcription of Rik-201 and Rik-203.Conclusions: These findings identify the functional role of Rik-201 and Rik-203 in facilitating neural differentiation and further brain development,and elucidate the underlying miRNAs-Sox6-associated molecular mechanisms.