LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF

Abstract

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

Data Sharing Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethical Statement

All animal procedures were performed in accordance with the Guide for Care and Use of Laboratory Animals from the National Health Research Institutes and Recommendations on Animal Care from the Chinese Neuroscience Society. All of the animal experiments were endorsed by the Institutional Animal Care and Use Committee of Xiangyang Central Hospital (Approval Number: 2017101305; Approval date: October 13, 2017).

Disclosure

The authors declare that they have no competing interests.

Co-first authors: Yao Yao, Xuesong Wang.