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

• 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: competitive endogenous RNA; epilepsy; KCNQ3; lncRNA GAS5; microRNA‐135a‐5p
• Online Access: https://doi.org/10.1002/kjm2.12102
• ISSN: 1607-551X; 2410-8650

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.