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LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-11-09 , DOI: 10.2147/dddt.s256319
Yao Yao 1 , Xuesong Wang 1 , Jin Gao 1
Affiliation  

Objective: Widely used in anesthesia, ketamine is reported to induce neurotoxicity in patients. This study aimed to investigate the molecular regulatory mechanism of long non-coding RNA (lncRNA) KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in ameliorating ketamine-induced neural injury.
Materials and Methods: Sprague–Dawley rats were intraperitoneally injected with ketamine to induce neuronal injury. PC-12 cells treated with ketamine were used as the cell model. Ketamine-induced aberrant expression of KCNQ1OT1, miR-206 and brain-derived neurotrophic factor (BDNF) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of KCNQ1OT1 and miR-206 on ketamine-induced neural injury in PC-12 cells were then examined by MTT and LDH assay. The regulatory relationships between KCNQ1OT1 and miR-206, and miR-206 and BDNF were detected by dual-luciferase reporter assay.
Results: Ketamine induced the apoptosis of neurons of the hippocampus in rats, and the apoptosis of PC-12 cells, accompanied by down-regulation of KCNQ1OT1 and BDNF expressions, and up-regulation of miR-206 expression. Overexpression of KCNQ1OT1 enhanced the resistance to apoptosis of PC-12 cells and significantly ameliorated ketamine-induced nerve injury, while transfection of miR-206 had opposite effects. Mechanistically, KCNQ1OT1 could target miR-206 and reduce its expression level, in turn indirectly increase the expression level of BDNF, and play a protective role in neural injury.
Conclusion: KCNQ1OT1/miR-206/BDNF axis is demonstrated to be an important regulatory mechanism in regulating ketamine-induced neural injury. Our study helps to clarify the mechanism by which ketamine exerts its toxicological effects and provides clues for the neuroprotection during anesthesia.

Keywords: ketamine, neural injury, lncRNA KCNQ1OT1, miR-206, BDNF


中文翻译:

LncRNA KCNQ1OT1 Sponges miR-206 通过上调 BDNF 改善麻醉诱导的神经损伤

目的:广泛用于麻醉,据报道氯胺酮可引起患者的神经毒性。本研究旨在探讨长链非编码 RNA (lncRNA) KCNQ1 反链/反义转录本 1 (KCNQ1OT1) 在改善氯胺酮诱导的神经损伤中的分子调控机制。
材料和方法:Sprague-Dawley 大鼠腹腔注射氯胺酮以诱导神经元损伤。用氯胺酮处理的 PC-12 细胞用作细胞模型。通过定量实时聚合酶链反应 (qRT-PCR) 检测氯胺酮诱导的 KCNQ1OT1、miR-206 和脑源性神经营养因子 (BDNF) 的异常表达。然后通过MTT和LDH测定检查KCNQ1OT1和miR-206对氯胺酮诱导的PC-12细胞神经损伤的影响。采用双荧光素酶报告基因检测KCNQ1OT1与miR-206、miR-206与BDNF之间的调控关系。
结果:氯胺酮可诱导大鼠海马神经元凋亡和PC-12细胞凋亡,同时下调KCNQ1OT1和BDNF表达,上调miR-206表达。KCNQ1OT1的过表达增强了PC-12细胞的抗凋亡能力,显着改善了氯胺酮诱导的神经损伤,而转染miR-206则相反。机制上,KCNQ1OT1可以靶向miR-206并降低其表达水平,进而间接增加BDNF的表达水平,在神经损伤中发挥保护作用。
结论:KCNQ1OT1/miR-206/BDNF 轴被证明是调节氯胺酮诱导的神经损伤的重要调节机制。我们的研究有助于阐明氯胺酮发挥毒理学作用的机制,并为麻醉期间的神经保护提供线索。

关键词:氯胺酮,神经损伤,lncRNA KCNQ1OT1,miR-206,BDNF
更新日期:2020-11-09
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