LncRNA UCA1 inhibits epilepsy and seizure-induced brain injury by regulating miR-495/Nrf2-ARE signal pathway

被引:67
作者
Geng, Jie-feng [1 ]
Liu, Xing [2 ]
Zhao, Hai-biao [1 ]
Fan, Wen-fei [1 ]
Geng, Jun-jie [1 ]
Liu, Xian-zhi [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Neurosurg, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Anesthesiol, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
lncRNA UCA1; miR-495; Nrf2-ARE pathway; Brain injury; NONCODING RNA UCA1; LONG; RESISTANCE; EXPRESSION; APOPTOSIS; MODELS; DAMAGE;
D O I
10.1016/j.biocel.2018.03.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Both LncRNA UCA1 and miR-495 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced brain injury. Methods: In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by qRT-PCR and western blot, respectively. The hippocampal neurons were isolated from hippocampal tissues, and treated with magnesium-free (MGF) physiological solution for epileptiform activity induction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Flow cytometry was used to analyze the cell apoptosis. Dual luciferase reporter assay was performed to determine the interaction between miR-495 and Nrf2 in HEK 293 cells. Results: The IncRNA UCA1 and Nrf2 were down-regulated in epileptiform hippocampal tissues and neurons, while the miR-495 was up-regulated. Over-expression of UCA1 inhibited apoptosis of hippocampal neurons by suppressing miR-495. MiR-495 negatively regulated Nrf2. UCA1 inhibited apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway. UCA1 suppressed pilocarpine-induced epilepsy in rat. Conclusion: LncRNA UCA1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-495/Nrf2-ARE pathway, and thereby inhibiting brain injury induced by seizure.
引用
收藏
页码:133 / 139
页数:7
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