LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3 beta-mediated neural differentiation
LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3 beta-mediated neural differentiation
复制标题
LncRNA Rik-203 通过 microRNA-101a-3p 和 GSK-3 β 介导的神经分化导致麻醉神经毒性
DOI：
10.1038/s41598-019-42991-4
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Jiang Hong
中科院分区：
文献类型：
--
作者：
Zhang Lei;Yan Jia;Liu Qidong;Xie Zhongcong;Jiang Hong
麻醉神经毒性的机制在很大程度上仍有待确定。长非编码 RNA (LncRNA) 对神经分化的影响及其潜在机制尚不清楚。因此，我们鉴定了 LncRNA Rik-203 (C130071C03Rik)，并研究了它在神经分化中的作用及其与麻醉剂七氟烷、miRNA 和 GSK-3β 的相互作用。我们发现海马中 Rik-203 的水平高于其他组织，并且在神经分化过程中增加。七氟醚降低了 Rik-203 的水平。 Rik-203 敲除降低了神经祖细胞标记物 Sox1 和 Nestin 的 mRNA 水平，并减少了 Sox1 阳性细胞的数量。 RNA-RNA Pull-down 显示 miR-101a-3p 与 Rik-203 高度结合。最后，七氟烷、Rik-203 敲低和 miR-101a-3p 过表达均降低了 GSK-3β 水平。这些数据表明 Rik-203 通过抑制 miR-101a-3p 降低 GSK-3β 水平的能力来促进神经分化，并且 LncRNA 将作为麻醉神经毒性的机制。
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.