Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Abstract Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell model...

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Main Authors: Bao‐Guang Li, Wen‐Juan Wu, Hua‐Cheng Zheng, Hua‐Fang Yang, Yue‐Xian Zuo, Xiao‐Pu Cui
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Kaohsiung Journal of Medical Sciences
Subjects:
Online Access:https://doi.org/10.1002/kjm2.12102
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spelling doaj-e23cf80121c24ef8b33b5f9256eeab012020-11-25T01:11:46ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502019-09-0135952753410.1002/kjm2.12102Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsyBao‐Guang Li0Wen‐Juan Wu1Hua‐Cheng Zheng2Hua‐Fang Yang3Yue‐Xian Zuo4Xiao‐Pu Cui5Department of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaDepartment of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaDepartment of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaDepartment of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaDepartment of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaDepartment of Neurology Children's Hospital of Hebei Province Shijiazhuang Hebei ChinaAbstract Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.https://doi.org/10.1002/kjm2.12102competitive endogenous RNAepilepsyKCNQ3lncRNA GAS5microRNA‐135a‐5p
collection DOAJ
language English
format Article
sources DOAJ
author Bao‐Guang Li
Wen‐Juan Wu
Hua‐Cheng Zheng
Hua‐Fang Yang
Yue‐Xian Zuo
Xiao‐Pu Cui
spellingShingle Bao‐Guang Li
Wen‐Juan Wu
Hua‐Cheng Zheng
Hua‐Fang Yang
Yue‐Xian Zuo
Xiao‐Pu Cui
Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
Kaohsiung Journal of Medical Sciences
competitive endogenous RNA
epilepsy
KCNQ3
lncRNA GAS5
microRNA‐135a‐5p
author_facet Bao‐Guang Li
Wen‐Juan Wu
Hua‐Cheng Zheng
Hua‐Fang Yang
Yue‐Xian Zuo
Xiao‐Pu Cui
author_sort Bao‐Guang Li
title Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
title_short Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
title_full Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
title_fullStr Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
title_full_unstemmed Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy
title_sort long noncoding rna gas5 silencing inhibits the expression of kcnq3 by sponging mir‐135a‐5p to prevent the progression of epilepsy
publisher Wiley
series Kaohsiung Journal of Medical Sciences
issn 1607-551X
2410-8650
publishDate 2019-09-01
description Abstract Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.
topic competitive endogenous RNA
epilepsy
KCNQ3
lncRNA GAS5
microRNA‐135a‐5p
url https://doi.org/10.1002/kjm2.12102
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