【罂粟摘要】lncRNA Xist介导miR-98-5p/EDEM1信号轴调控七氟烷诱导的新生小鼠社交和情绪障碍
lncRNA Xist介导miR-98-5p/EDEM1信号轴调控七氟烷诱导的新生小鼠社交和情绪障碍
贵州医科大学 高鸿教授课题组
翻译：曹莹 编辑：佟睿 审校：曹莹
长链非编码RNA (lncRNA) x -非活性特异性转录本(Xist)参与细胞凋亡和炎症性损伤。本研究通过新生小鼠和海马神经元实验来评估lncRNA Xist在七氟烷诱导的社交、情绪障碍及神经元凋亡中的作用。行七氟烷暴露造模后检测新生小鼠的社交表现、情绪测试和lncRNA Xist以及microRNA (miR)-98-5p的表达水平。与此同时，我们还研究了抑制lncRNA Xist表达对神经元凋亡和内质网应激(ER)的影响。随后，我们探索了lncRNA Xist、miR-98-5p和ER降解增强α-甘露糖苷酶样蛋白1(EDEM1)之间的关系。我们的研究结果显示，新生小鼠经过七氟烷暴露处理后，lncRNA Xist表达增加，miR-98-5p表达减少，出现社交和情感障碍。此外，通过在体和体外细胞实验，抑制lncRNA Xist可以改善七氟烷诱导的社交和情感障碍，减少七氟烷诱导的神经元凋亡和内质网应激。此外，lncRNA Xist负调控miR-98-5p的表达，并通过海绵化miR-98-5p参与七氟烷诱导的神经元凋亡和内质网应激；EDEM1被鉴定为miR-98-5p的靶点。我们的研究提示，敲低lncRNA Xist表达可以通过靶向miR-98-5p/ EDEM1轴抑制神经元凋亡和内质网应激，从而改善七氟烷诱导的新生小鼠社交和情感障碍。
lncRNA Xist regulates sevoflflurane-induced social and emotional impairment by modulating miR-98-5p/EDEM1 signaling axis in neonatal mice
Long non-coding RNA (lncRNA) X-inactive specifific transcript (Xist) is involved in apoptosis and inflflammatory injury. This study aimed to assess the role of lncRNA Xist in sevoflfluraneinduced social and emotional impairment and neuronal apoptosis in neonatal mice and hippocampal neuronal cells. The performance in social and emotional tests and the expression levels of lncRNA Xist and microRNA (miR)-98-5p after sevoflflurane exposure were measured. Moreover, the effects of suppression of lncRNA Xist on neuronal apoptosis and endoplasmic reticulum (ER) stress were determined. Subsequently, the association among lncRNA Xist, miR-98-5p, and ER degradation-enhancing a-mannosidase-like 1 protein (EDEM1) was explored. Our results showed that lncRNA Xist increased, miR- 98-5p decreased, and social and emotional impairment appeared after sevoflflurane exposure. Furthermore, suppression of lncRNA Xist improved sevoflflurane-induced social and emotional impairment and reduced sevoflflurane-induced neuronal apoptosis and ER stress in vivo and in vitro. Moreover, lncRNA Xist negatively regulated miR-98-5p expression, and it contributed to sevoflflurane-induced neuronal apoptosis and ER stress by sponging miR-98-5p. Additionally, EDEM1 was identifified as a target of miR-98-5p. Our fifindings revealed that the knockdown of lncRNA Xist ameliorates sevoflfluraneinduced social and emotional impairment through inhibiting neuronal apoptosis and ER stress by targeting the miR-98-5p/ EDEM1 axis.
原始文献来源：Lili Xu, Qi Xu, Shaobing Dai, et al. lncRNA Xist regulates sevoflflurane-induced social and emotional impairment by modulating miR-98-5p/EDEM1 signaling axis in neonatal mice. [J]Molecular Therapy: Nucleic Acids.DOI:10.1016/j.omtn.2021.04.010.