The miR-34a-5p Promotes Hippocampal Neuronal Ferroptosis in Epilepsy by Regulating SIRT1

Epilepsy, one of the most prevalent neurological disorders, affects approximately 50 million individuals worldwide. MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of target genes at the post-transcriptional level by interacting with specific sequences of the target genes in a complementary manner, thus affecting a variety of biological processes. miR-34a-5p has been shown to be involved in the regulation of cellular ferroptosis, and we aimed to explore its expression in epilepsy and its mechanism of action in epileptic ferroptosis. Techniques such as Hoechst and eosin staining, Nissl staining, real-time quantitative polymerase chain reaction assays, Western blotting, immunofluorescence, dualluciferase reporter assays, and Lipid peroxidation-related assays were used to explore epilepsy pathogenesis. Markedly elevated miR-34a-5p expression levels were observed in the hippocampal regions of epileptic rats and magnesium-free hippocampal neuronal cultures. SIRT1 was identified as a direct target of miR-34a-5p. miR-34a-5p suppression reduced ACSL4, wnt3a, β-catenin, cyclin D1, iron ion, MDA and reactive oxygen species levels, while upregulating SIRT1, GPX4, Ferritin, and GSH expression levels. miR-34a-5p might modulate the Wnt/β-catenin signaling pathway, implicated in neuronal ferroptosis by directly targeting SIRT1. Our findings offer a potential therapeutic target to inhibit epilepsy progression.