Overexpressed microRNA-494 represses RIPK1 to attenuate hippocampal neuron injury in epilepsy rats by inactivating the NF-κB signaling pathway

Abstract

Objective: The effects of microRNAs (miRNAs) have been identified in epilepsy (Ep) in recent years, our research was focused on the functions of miR-494 in Ep and its inner mechanisms. Methods: The Ep modeled rats induced by lithium chloride-pilocarpine were treated with agomir-miR-494 or RIPK1-siRNA. The pathology of rat hippocampal tissues was observed. Expression of miR-494, receptor-interacting protein kinase 1 (RIPK1) and nuclear factor-kappaB (NF-κB) p65 was assessed by RT-qPCR and Western blot analysis. The hippocampal neurons of epileptic rats were successfully modeled, which were transfected with miR-494 mimics or RIPK1-siRNA to determine neurons' proliferation ability and cell apoptosis. The target relation between miR-494 and RIPK1 was measured by bioinformatics website and dual luciferase gene reporter assay. Results: The expression of miR-494 was reduced, while the expression of RIPK1 and NF-κB p65 was amplified in hippocampus of Ep rats. Elevated miR-494 repressed the expression of RIPK1 to ameliorate the hippocampal neuron injury, accelerate neuronal proliferation, and restrain neuronal apoptosis via inactivating the NF-κB signaling pathway, causing a deceleration of Ep development. Furthermore, amplified RIPK1 was able to reverse the amelioration of neuronal injury in Ep rats which was contributed by upregulated miR-494. Conclusion:We found in this study that elevated miR-494 repressed RIPK1, causing an inactivation of the NF-κB signaling pathway and acceleration of cell proliferation, and suppression of apoptosis of hippocampal neurons in Ep rats, thereby attenuating the neuron injury and Ep development. Our research may provide novel targets for the therapy of Ep.

PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway

“…Losmapimod was shown to exert protective effects on epilepsy by reducing neuron loss through the suppression of MAPK phosphorylation. Qi et al ( 31 ) demonstrated that miR-494 inhibits receptor-interacting serine/threonine-protein kinase 1 to suppress the apoptosis of hippocampal neurons and reduce the neuronal damage in epileptic rats by deactivating the NF-κB pathway. In addition, it has been reported that rehmannioside A attenuates depression by suppressing ER stress and apoptosis in the hippocampus of chronic unpredictable mild stress-induced rats by regulating MAPK signaling ( 32 ).…”

Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products

“…Interleukin-27 upregulates miR-6852-5p and causes necrosis in cervical cancer cells by inhibiting Forkhead box protein M1 (FOXM1) expression [ 76 ], with the FOXM1 being suppressed by FOXO3a [ 138 ]. Upregulated miR-494-3p inhibits the expression of receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in epilepsy rats [ 139 ], which is a necroptosis regulator [ 140 ]. Moreover, miR-494-3p targets the c-Myc and SIRT1 genes in ovarian cancer (OVCAR3) cells [ 87 ].…”

ON THE ROLE OF TUMOR NECROSIS FACTOR-ALPHA (TNF-α) AND NUCLEAR FACTOR p-NF-κB IN THE PENTYLENETETRAZOLE KINDLING PATHOGENESIS

“…Підтвердженням цього припущення є дані щодо нейропротекторного ефекту інактивації клітин мікроглії та інгібування NF-kB на моделі генералізованої епілепсії, спричиненої каїновою кислотою [13]. Надмірна експресія мікроРНК, яка інактивує сигнальний шлях NF-kB, зменшує пошкодження нейронів гіпокампу при епілепсії, зменшує реакцію активації мікроглії [14].…”