lncRNA Xist regulates sevoflurane-induced social and emotional impairment by modulating miR-98-5p/EDEM1 signaling axis in neonatal mice
| Autor: | Hui Wu, Lili Xu, Jiaqian Xie, Xinzhong Chen, Cuicui Jiao, Yingying Tang, Shaobing Dai, Qi Xu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
sevoflurane RM1-950 Biology 03 medical and health sciences 0302 clinical medicine neurotoxicity Drug Discovery microRNA medicine Gene knockdown apoptosis Neurotoxicity RNA medicine.disease Cell biology Trib3 lncRNA Xist miR-98-5p 030104 developmental biology Apoptosis TRIB3 030220 oncology & carcinogenesis Unfolded protein response Molecular Medicine Original Article XIST Therapeutics. Pharmacology EDEM1 CHOP |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 24, Iss, Pp 939-950 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| DOI: | 10.1016/j.omtn.2021.04.010 |
| Popis: | 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 in vivo and in vitro. 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. Graphical abstract Chen and colleagues proved that lncRNA XIST knockdown can ameliorate sevoflurane-induced social and emotional impairment through inhibiting neuron apoptosis and endoplasmic reticulum stress by targeting the miR-98-5p/EDEM1 axis. The understanding of cell death mechanisms in anesthesia-caused social and emotional impairment is vital to improve interventions in patients and reduce neural dysfunctionality. |
| Databáze: | OpenAIRE |
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