Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel

Abstract

Background and purpose Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non‐coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. Methods MiR‐146a, miR‐155 and miR‐132 were quantified by real‐time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2–ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. Results Serum levels of miR‐146a and miR‐155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR‐146a, miR‐155 and miR‐132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. Conclusions Our results indicate that miR‐146a, miR‐155 and miR‐132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients’ quality of life through earlier diagnosis and a more precise prognosis.

The Progress in Diagnosis and Treatment of Exosomes and MicroRNAs on Epileptic Comorbidity Depression

“…On the other hand, for genetic generalized epilepsies, it may be more connection with microRNAs. Martins-Ferreira et al found that miR-146a, miR-155, and miR-132 may partake in genetic generalized epilepsies(GGE) epileptogenesis and they reported that the three circulating microRNAs have potential value to be GGE biomarker (37). In particular, the striking up-regulation of miR-132 in epilepsy has been described in several experimental articles (38)(39)(40).…”

MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

“…Serum of miR-146a and miR-155 levels are also significantly upregulated in genetic generalized epilepsy patients. Martins-Ferreira et al (2020) suggested that the combined serum levels of miR-132, miR-146a, and miR-155 could discriminate between genetic generalized epilepsy patients and controls with high specificity and sensitivity.…”

Pharmacological and Therapeutic Approaches in the Treatment of Epilepsy

“…Currently, with the emerging research of epigenetic biomarkers, MicroRNAs (miRNAs) have been assumed to play a significant role. MiRNA molecules 19-25 nucleotides long regulate gene expression as post-transcriptional modifiers [ 11 ]. Differential expression of more than 100 miRNAs has been reported in epilepsy.…”

“…Differential expression of more than 100 miRNAs has been reported in epilepsy. Among them, because of their predominant role in biological processes related to epilepsy, such as neurodegeneration, neuronal growth, and neuroinflammation, miR-132, miR-155, and miR-146a have been highlighted primarily [ 11 ]. Some cases of genetic mutations result in the core symptom of epilepsy, while changes in a few of the genes are responsible for malformations in the gross development of the brain that cause seizures.…”