Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China; Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, 215002, Jiangsu, China.
Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, 215002, Jiangsu, China.
Exp Cell Res. 2021 Jan 1;398(1):112384. doi: 10.1016/j.yexcr.2020.112384. Epub 2020 Nov 17.
Epilepsy is one of the most common neurological diseases with spontaneous recurrent seizures. Long noncoding RNAs (lncRNAs) are crucial modulators in numerous diseases, including epilepsy. However, the functional role and potential mechanism of lncRNA Nespas in epilepsy remain unknown. Our study clarified that Nespas was underexpressed in epileptiform hippocampal tissues and neurons. Furthermore, Nespas promoted hippocampal neuron viability and proliferation, and inhibited hippocampal neuron apoptosis. Mechanistically, Nespas interacted with microRNA 615-3p (miR-615-3p) in epileptiform hippocampal neurons. 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) was a downstream target of miR-615-3p, and Nespas elevated Psmd11 expression via competitively binding to miR-615-3p in epileptiform hippocampal neurons. In addition, rescue assays suggested that Nespas promoted hippocampal neuron viability and proliferation, and suppressed hippocampal neuron apoptosis by upregulation of Psmd11. Furthermore, Nespas suppressed the PI3K/Akt/mTOR pathway via upregulating Psmd11 in epileptiform hippocampal neurons. This report explored the function and regulatory mechanism of Nespas in epileptiform hippocampal neurons for the first time. Our findings revealed that Nespas suppressed the apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway via upregulation of Psmd11 at a miR-615-3p dependent way, indicating that Nespas may offer a new direction for the treatment of epilepsy.
癫痫是最常见的神经系统疾病之一，具有自发性复发性癫痫发作。长链非编码 RNA（lncRNA）是包括癫痫在内的许多疾病的重要调节因子。然而，lncRNA Nespas 在癫痫中的功能作用和潜在机制尚不清楚。我们的研究表明，Nespas 在癫痫样海马组织和神经元中表达下调。此外，Nespas 促进海马神经元存活和增殖，抑制海马神经元凋亡。机制上，Nespas 在癫痫样海马神经元中与 microRNA 615-3p（miR-615-3p）相互作用。26S 蛋白酶体非 ATP 酶调节亚基 11（Psmd11）是 miR-615-3p 的下游靶标，Nespas 通过与癫痫样海马神经元中的 miR-615-3p 竞争结合来上调 Psmd11 表达。此外，挽救实验表明，Nespas 通过上调 Psmd11 促进海马神经元存活和增殖，抑制海马神经元凋亡。此外，Nespas 通过上调 Psmd11 在癫痫样海马神经元中抑制 PI3K/Akt/mTOR 通路。本报告首次探讨了 Nespas 在癫痫样海马神经元中的功能和调节机制。我们的研究结果表明，Nespas 通过抑制 PI3K/Akt/mTOR 通路，上调 Psmd11 抑制癫痫样海马神经元凋亡，这表明 Nespas 可能为癫痫治疗提供新的方向。
