Xu Lili, Xu Qi, Dai Shaobing, Jiao Cuicui, Tang Yingying, Xie Jiaqian, Wu Hui, Chen Xinzhong
Department of Anesthesiology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
Mol Ther Nucleic Acids. 2021 Apr 16;24:939-950. doi: 10.1016/j.omtn.2021.04.010. eCollection 2021 Jun 4.
Long non-coding RNA (lncRNA) X-inactive specific transcript (Xist) is involved in apoptosis and inflammatory injury. This study aimed to assess the role of lncRNA Xist in sevoflurane-induced 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 sevoflurane 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 α-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 sevoflurane exposure. Furthermore, suppression of lncRNA Xist improved sevoflurane-induced social and emotional impairment and reduced sevoflurane-induced neuronal apoptosis and ER stress and . Moreover, lncRNA Xist negatively regulated miR-98-5p expression, and it contributed to sevoflurane-induced neuronal apoptosis and ER stress by sponging miR-98-5p. Additionally, EDEM1 was identified as a target of miR-98-5p. Our findings revealed that the knockdown of lncRNA Xist ameliorates sevoflurane-induced social and emotional impairment through inhibiting neuronal apoptosis and ER stress by targeting the miR-98-5p/EDEM1 axis.
长链非编码RNA(lncRNA)X染色体失活特异性转录本(Xist)参与细胞凋亡和炎症损伤。本研究旨在评估lncRNA Xist在新生小鼠和海马神经元细胞中七氟醚诱导的社交和情感障碍以及神经元凋亡中的作用。检测了七氟醚暴露后社交和情感测试中的表现以及lncRNA Xist和微小RNA(miR)-98-5p的表达水平。此外,还确定了抑制lncRNA Xist对神经元凋亡和内质网(ER)应激的影响。随后,探讨了lncRNA Xist、miR-98-5p和内质网降解增强α-甘露糖苷酶样蛋白1(EDEM1)之间的关联。我们的结果表明,七氟醚暴露后lncRNA Xist增加,miR-98-5p减少,并出现社交和情感障碍。此外,抑制lncRNA Xist改善了七氟醚诱导的社交和情感障碍,并减少了七氟醚诱导的神经元凋亡和ER应激。此外,lncRNA Xist负向调节miR-98-5p的表达,并通过海绵吸附miR-98-5p促进七氟醚诱导的神经元凋亡和ER应激。此外,EDEM1被确定为miR-98-5p的靶标。我们的研究结果表明,敲低lncRNA Xist通过靶向miR-98-5p/EDEM1轴抑制神经元凋亡和ER应激,从而改善七氟醚诱导的社交和情感障碍。