Knockdown of ZFAS1 Inhibits Hippocampal Neurons Apoptosis and Autophagy by Activating the PI3K/AKT Pathway via Up-regula
- PDF / 3,071,202 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 39 Downloads / 190 Views
ORIGINAL PAPER
Knockdown of ZFAS1 Inhibits Hippocampal Neurons Apoptosis and Autophagy by Activating the PI3K/AKT Pathway via Up‑regulating miR‑421 in Epilepsy Fan Hu1 · Liang Shao2 · Ji Zhang1 · Hong Zhang1 · An Wen1 · Ping Zhang1 Received: 18 February 2020 / Revised: 2 July 2020 / Accepted: 22 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Epilepsy is a common neurological disease. The dysregulated long noncoding RNAs (lncRNAs) are implicated in epileptogenesis. The aim of this research is to explore the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in status epilepticus (SE)-induced hippocampal neurons injury. SE mice model was established and primary hippocampal neurons were isolated. The expression levels of ZFAS1 and microRNA-421 (miR-421) were detected in hippocampus and hippocampal neurons via quantitative reverse transcription polymerase chain reaction. Hippocampal neurons viability, apoptosis and autophagy were analyzed via Cell Counting Kit-8, flow cytometry and western blot. The target relationship between ZFAS1 and miR-421 was analyzed via dual-luciferase reporter assay. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was blocked by LY294002 and related protein levels were detected via western blot. ZFAS1 expression was elevated in hippocampus and hippocampal neurons from SE mice. Knockdown of ZFAS1 increased SE hippocampal neurons viability and decreased apoptosis and autophagy. ZFAS1 could sponge miR-421. MiR-421 expression was declined in SE mice tissues and cells. Down-regulation of miR-421 abolished the suppressive effect of ZFAS1 knockdown on hippocampal neurons apoptosis and autophagy. Silencing of ZFAS1 induced activation of the PI3K/AKT pathway by up-regulating miR-421. Inhibition of the PI3K/AKT pathway reversed the effect of ZFAS1 knockdown on SE hippocampal neurons apoptosis and autophagy. Interference of ZFAS1 attenuated hippocampal neurons apoptosis and autophagy in SE by increasing miR-421 and activating the PI3K/AKT pathway, indicating a new mechanism for understanding the pathogenesis of SE. Keywords Epilepsy · Autophagy · Apoptosis · ZFAS1 · miR-421 · PI3K/AKT pathway
Introduction Epilepsy is a common neurological disorder impairing life quality of patients with status epilepticus (SE) [1]. Great advances have been gained on the development, prediction and treatment of epilepsy [2]. The effective strategy for epilepsy remains a challenge. The hippocampal damage and dysfunction of hippocampal neurons are implicated in the development of epilepsy [3, 4]. Therefore, exploring the * Ping Zhang [email protected] 1
Department of Neurology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, China
Department of Cardiology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, China
2
pathogenesis of hippocampal neurons dysfunction might be helpful to find out new target for the treatment of epilepsy. The dysreg
Data Loading...
