LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF
Yao Yao,* Xuesong Wang,* Jin Gao Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang 441021, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin GaoDepartment of Anesth...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2020-11-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/lncrna-kcnq1ot1-sponges-mir-206-to-ameliorate-neural-injury-induced-by-peer-reviewed-article-DDDT |
| _version_ | 1828959471939878912 |
|---|---|
| author | Yao Y Wang X Gao J |
| author_facet | Yao Y Wang X Gao J |
| author_sort | Yao Y |
| collection | DOAJ |
| description | Yao Yao,* Xuesong Wang,* Jin Gao Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang 441021, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin GaoDepartment of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Jingzhou Street No. 39, Xiangcheng District, Xiangyang 441021, Hubei, People’s Republic of ChinaTel +86 15897965817Email ji84174603@163.comObjective: 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 |
| first_indexed | 2024-12-14T09:08:24Z |
| format | Article |
| id | doaj.art-d207a1b2ac3d4b12ab65deb215d77761 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-14T09:08:24Z |
| publishDate | 2020-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-d207a1b2ac3d4b12ab65deb215d777612022-12-21T23:08:39ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-11-01Volume 144789480059065LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNFYao YWang XGao JYao Yao,* Xuesong Wang,* Jin Gao Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang 441021, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin GaoDepartment of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Jingzhou Street No. 39, Xiangcheng District, Xiangyang 441021, Hubei, People’s Republic of ChinaTel +86 15897965817Email ji84174603@163.comObjective: 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, BDNFhttps://www.dovepress.com/lncrna-kcnq1ot1-sponges-mir-206-to-ameliorate-neural-injury-induced-by-peer-reviewed-article-DDDTketamineneural injurylncrna kcnq1ot1mir-206bdnf |
| spellingShingle | Yao Y Wang X Gao J LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF Drug Design, Development and Therapy ketamine neural injury lncrna kcnq1ot1 mir-206 bdnf |
| title | LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF |
| title_full | LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF |
| title_fullStr | LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF |
| title_full_unstemmed | LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF |
| title_short | LncRNA KCNQ1OT1 Sponges miR-206 to Ameliorate Neural Injury Induced by Anesthesia via Up-Regulating BDNF |
| title_sort | lncrna kcnq1ot1 sponges mir 206 to ameliorate neural injury induced by anesthesia via up regulating bdnf |
| topic | ketamine neural injury lncrna kcnq1ot1 mir-206 bdnf |
| url | https://www.dovepress.com/lncrna-kcnq1ot1-sponges-mir-206-to-ameliorate-neural-injury-induced-by-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT yaoy lncrnakcnq1ot1spongesmir206toameliorateneuralinjuryinducedbyanesthesiaviaupregulatingbdnf AT wangx lncrnakcnq1ot1spongesmir206toameliorateneuralinjuryinducedbyanesthesiaviaupregulatingbdnf AT gaoj lncrnakcnq1ot1spongesmir206toameliorateneuralinjuryinducedbyanesthesiaviaupregulatingbdnf |