Down-regulation of Long Noncoding RNA MALAT1 Protects Hippocampal Neurons Against Excessive Autophagy and Apoptosis via the PI3K/Akt Signaling Pathway in Rats with Epilepsy

Abstract

Epilepsy is a common chronic brain disorder and is characterized by an enduring predisposition to generate seizures. The hippocampus is especially vulnerable to seizure-induced damage. In this study, we explore the ability of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) to influence the autophagy and apoptosis of hippocampal neurons in epilepsy and the underlying mechanism involving the PI3K/Akt signaling pathway. Seventy-two Sprague-Dawley rats were assigned to normal, sham, Ep, Ep + si-NC, Ep + si-MALAT1, and Ep + si-MALAT1 + LY groups. Fluorescence in situ hybridization kit was employed to determine the MALAT1 in the brain tissues. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine the expression of MALAT1, mRNAs, and proteins. The autophagy of hippocampal neurons was evaluated under a transmission electron microscope and their apoptosis was evaluated using TUNEL staining. We found that MALAT1 and c-Met were enriched while microRNA-101 (miR-101) decreased in rats with epilepsy. The demonstration showed that MALAT1 binds to miR-101, thus regulating c-Met. In rats with epilepsy, MALAT1 depletion mediated by anti-MALAT1 siRNA resulted in activation of PI3K/Akt signaling pathway and loss of hippocampal neurons. LY294002, an inhibitor of PI3K/Akt signaling pathway, could reverse the events caused by MALAT1 knockdown. Taken together, these findings indicate that down-regulation of MALAT1 activates the PI3K/Akt signaling pathway to protect hippocampal neurons against autophagy and apoptosis in rats with epilepsy.

MiR‐101 relates to chronic peripheral neuropathic pain through targeting KPNB1 and regulating NF‐κB signaling

“…26 MiR-101 is a multiple function molecule, which has been found play a role in maintaining the homeostasis of the neuro system, and abnormal miR-101 level has been identified relates to pathophysiological conditions including spinocerebellar ataxia type 1 and Alzheimer's disease. 18,27,28 miR-101 also functions as an important regulator during the immune response in macrophages. 29 However, roles of miR-101 in the neuroimmune system is still unknown.…”

Role of GPX4-Mediated Ferroptosis in the Sensitivity of Triple Negative Breast Cancer Cells to Gefitinib

“…Image Pro Plus 6.0 (media cybernetics, USA) was used to quantify the gray level of each band, and βactin was used as an internal reference. Each experiment was repeated three times [25].…”

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

“…Following the removal of all blood, the rats stopped autonomous breathing and heartbeat. After the confirmation of rat death, the cranium was opened to extract the brain immediately [7]. The brains were fixed into Bouin's fixative solution for 24 h, dehydrated by gradient alcohol, put into dimethylbenzene, and embedded in paraffin.…”

“…Findings of Wu et al indicated that lncRNA MALAT1 down-regulation could protect hippocampal neurons against apoptosis and autophagy through promoting the PI3K/Akt signaling pathway in rats with epilepsy [7]. LncRNA nuclear-enriched abundant transcript 1 (NEAT1) is a recently observed crucial factor of nuclear paraspeckles, which has been validated to perform as an oncogene in assorted human cancers, such as pancreatic cancer, colon cancer, glioma and hepatocellular carcinoma [8][9][10][11].…”