Downregulation of MicroRNA-34c-5p facilitated neuroinflammation in drug-resistant epilepsy

• Published in: Brain research Vol. 1749; p. 147130
• Main Authors: Fu, Meng, Tao, Jie, Wang, Dongdong, Zhang, Zhiping, Wang, Xiaoli, Ji, Yonghua, Li, Zhiping
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2020
• Subjects: Drug-resistant epilepsy; HMGB1; miR-34c-5p; Neurology; Neuron loss; Pediatric; Neuron loss; EEG; VPA; 3′-UTR; HMGB1; TLE; AEDs; SE; Drug-resistant epilepsy; DRE; KA; DSE; miR-34c-5p; Pediatric; drug-resistant epilepsy; antiepileptic drugs; temporal lobe epilepsy; drug-sensitive epilepsy; kainic acid; valproic acid; electroencephalogram; status epilepticus; 3′-untranslated regions
• ISSN: 0006-8993; 1872-6240; 1872-6240
• DOI: 10.1016/j.brainres.2020.147130

•MiR-34c-5p was down-regulated in drug-resistant epilepsy.•Down-regulation of miR-34c-5p led to increased expression of HMGB1 and IL-1β.•Aberrant expression of these molecules contributes to loss of hippocampal neurons.•MiR-34c-5p could be a potential therapeutic target for drug-resistant epilepsy. Drug-resistant epilepsy patients has aberrant inflammatory mediator levels. However, the mechanism of which is remains unillustrated. Here the molecular mechanism underlying the neuroinflammatory process in patients with drug-resistant epilepsy were investigated. Bioinformatics analysis revealed that miR-34c-5p was significantly downregulated in patients with drug-resistant epilepsy, compared to control population. Then, luciferase reporter assays indicated that HMGB1, inflammation-related mediators, was the target gene of miR-34c-5p. The kainic acid-induced epileptic rats were established and divided into drug-sensitive epilepsy and drug-resistant epilepsy according to their seizure behavior and EEG after antiepileptic drug administration. Downregulation of miR-34c-5p, elevated expression of HMGB1 and IL-1β had been found in rats with drug-resistant epilepsy, compared to drug-sensitive epilepsy rats. Aggravated hippocampal neuron loss was demonstrated in rats with drug-resistant epilepsy. The results from epileptic rats were subsequently validated from children with drug-resistant epilepsy. Analysis manifested that miR-34c-5p was obviously decreased, while HMGB1 was increased on serum of children with drug-resistant epilepsy. Our study highlights that decreased miR-34c-5p in drug-resistant epilepsy exacerbates neuroinflammation, which aggravates hippocampal neuron loss in epileptogenesis. Thus, miR-34c-5p could be considered as a potential noninvasive biomarker and shed novel light on the development of an effective therapeutic strategy for children with drug-resistant epilepsy in the future.